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Fulltext Pathophysiological Perspective of Osteoarthritis

Yunus MHM, Nordin A, Kamal H

Medicina (Kaunas), 2020 Nov 16;56(11).
PMID: 33207632 DOI: 10.3390/medicina56110614

Osteoarthritis (OA) is the most well-known degenerative disease among the geriatric and is a main cause of significant disability in daily living. It has a multifactorial etiology and is characterized by pathological changes in the knee joint structure including cartilage erosion, synovial inflammation, and subchondral sclerosis with osteophyte formation. To date, no efficient treatment is capable of altering the pathological progression of OA, and current therapy is broadly divided into pharmacological and nonpharmacological measures prior to surgical intervention. In this review, the significant risk factors and mediators, such as cytokines, proteolytic enzymes, and nitric oxide, that trigger the loss of the normal homeostasis and structural changes in the articular cartilage during the progression of OA are described. As the understanding of the mechanisms underlying OA improves, treatments are being developed that target specific mediators thought to promote the cartilage destruction that results from imbalanced catabolic and anabolic activity in the joint.

Matched MeSH terms: Cartilage, Articular*
Fulltext Congenital rudimentary medial meniscus--report of a case of development arrest of medial meniscus

Aranha A, Nor M

Singapore Med J, 1990 Apr;31(2):189-90.
PMID: 2371587

We present an unusual case, where the medial meniscus does not coincide with the embryological development of the formation of a discoid cartilage. A fairly, careful perusal of English literature since 1945 to date makes us feel that the following case merits recording. The meniscus had a normal anterior horn attached to the intercondylar area, in front of the anterior cruciate ligament. Medially, it was attached to the capsule and the condylar surface of the medial tibial plateau. The posterior horn was rounded, smooth, and floating free of any attachments. It was approximately 2 cms in length, semilunar in shape, and extended posteriorly up to the anterior margin of the medial collateral ligament. The rest of the medial tibial plateau had no other protective covering.

Matched MeSH terms: Cartilage, Articular/abnormalities*; Cartilage, Articular/embryology; Cartilage, Articular/pathology
The metabolic dynamics of cartilage explants over a long-term culture period

Moo EK, Osman NA, Pingguan-Murphy B

Clinics (Sao Paulo), 2011;66(8):1431-6.
PMID: 21915496

INTRODUCTION: Although previous studies have been performed on cartilage explant cultures, the generalized dynamics of cartilage metabolism after extraction from the host are still poorly understood due to differences in the experimental setups across studies, which in turn prevent building a complete picture.
METHODS: In this study, we investigated the response of cartilage to the trauma sustained during extraction and determined the time needed for the cartilage to stabilize. Explants were extracted aseptically from bovine metacarpal-phalangeal joints and cultured for up to 17 days.
RESULTS: The cell viability, cell number, proteoglycan content, and collagen content of the harvested explants were analyzed at 0, 2, 10, and 17 days after explantation. A high percentage of the cartilage explants were found to be viable. The cell density initially increased significantly but stabilized after two days. The proteoglycan content decreased gradually over time, but it did not decrease to a significant level due to leakage through the distorted peripheral collagen network and into the bathing medium. The collagen content remained stable for most of the culture period until it dropped abruptly on day 17.
CONCLUSION: Overall, the tested cartilage explants were sustainable over long-term culture. They were most stable from day 2 to day 10. The degradation of the collagen on day 17 did not reach diseased levels, but it indicated the potential of the cultures to develop into degenerated cartilage. These findings have implications for the application of cartilage explants in pathophysiological fields.

Matched MeSH terms: Cartilage, Articular/cytology; Cartilage, Articular/drug effects; Cartilage, Articular/metabolism*; Cartilage, Articular/chemistry
Comparative efficacy of stem cells and secretome in articular cartilage regeneration: a systematic review and meta-analysis

Muhammad SA, Nordin N, Mehat MZ, Fakurazi S

Cell Tissue Res, 2019 Feb;375(2):329-344.
PMID: 30084022 DOI: 10.1007/s00441-018-2884-0

Articular cartilage defect remains the most challenging joint disease due to limited intrinsic healing capacity of the cartilage that most often progresses to osteoarthritis. In recent years, stem cell therapy has evolved as therapeutic strategies for articular cartilage regeneration. However, a number of studies have shown that therapeutic efficacy of stem cell transplantation is attributed to multiple secreted factors that modulate the surrounding milieu to evoke reparative processes. This systematic review and meta-analysis aim to evaluate and compare the therapeutic efficacy of stem cell and secretome in articular cartilage regeneration in animal models. We systematically searched the PubMed, CINAHL, Cochrane Library, Ovid Medline and Scopus databases until August 2017 using search terms related to stem cells, cartilage regeneration and animals. A random effect meta-analysis of the included studies was performed to assess the treatment effects on new cartilage formation on an absolute score of 0-100% scale. Subgroup analyses were also performed by sorting studies independently based on similar characteristics. The pooled analysis of 59 studies that utilized stem cells significantly improved new cartilage formation by 25.99% as compared with control. Similarly, the secretome also significantly increased cartilage regeneration by 26.08% in comparison to the control. Subgroup analyses revealed no significant difference in the effect of stem cells in new cartilage formation. However, there was a significant decline in the effect of stem cells in articular cartilage regeneration during long-term follow-up, suggesting that the duration of follow-up is a predictor of new cartilage formation. Secretome has shown a similar effect to stem cells in new cartilage formation. The risk of bias assessment showed poor reporting for most studies thereby limiting the actual risk of bias assessment. The present study suggests that both stem cells and secretome interventions improve cartilage regeneration in animal trials. Graphical abstract ᅟ.

Matched MeSH terms: Cartilage, Articular/cytology*; Cartilage, Articular/metabolism*
Fulltext Potential of Exosomes as Cell-Free Therapy in Articular Cartilage Regeneration: A Review

Ng CY, Chai JY, Foo JB, Mohamad Yahaya NH, Yang Y, Ng MH, et al.

Int J Nanomedicine, 2021;16:6749-6781.
PMID: 34621125 DOI: 10.2147/IJN.S327059

Treatment of cartilage defects such as osteoarthritis (OA) and osteochondral defect (OCD) remains a huge clinical challenge in orthopedics. OA is one of the most common chronic health conditions and is mainly characterized by the degeneration of articular cartilage, shown in the limited capacity for intrinsic repair. OCD refers to the focal defects affecting cartilage and the underlying bone. The current OA and OCD management modalities focus on symptom control and on improving joint functionality and the patient's quality of life. Cell-based therapy has been evaluated for managing OA and OCD, and its chondroprotective efficacy is recognized mainly through paracrine action. Hence, there is growing interest in exploiting extracellular vesicles to induce cartilage regeneration. In this review, we explore the in vivo evidence of exosomes on cartilage regeneration. A total of 29 in vivo studies from the PubMed and Scopus databases were identified and analyzed. The studies reported promising results in terms of in vivo exosome delivery and uptake; improved cartilage morphological, histological, and biochemical outcomes; enhanced subchondral bone regeneration; and improved pain behavior following exosome treatment. In addition, exosome therapy is safe, as the included studies documented no significant complications. Modifying exosomal cargos further increased the cartilage and subchondral bone regeneration capacity of exosomes. We conclude that exosome administration is a potent cell-free therapy for alleviating OA and OCD. However, additional studies are needed to confirm the therapeutic potential of exosomes and to identify the standard protocol for exosome-based therapy in OA and OCD management.

Matched MeSH terms: Cartilage, Articular*
Fulltext Clinical Potential of Cellular Material Sources in the Generation of iPSC-Based Products for the Regeneration of Articular Cartilage

Eremeev A, Pikina A, Ruchko Y, Bogomazova A

Int J Mol Sci, 2023 Sep 22;24(19).
PMID: 37833856 DOI: 10.3390/ijms241914408

Inflammatory joint diseases, among which osteoarthritis and rheumatoid arthritis are the most common, are characterized by progressive degeneration of the cartilage tissue, resulting in the threat of limited or lost joint functionality in the absence of treatment. Currently, treating these diseases is difficult, and a number of existing treatment and prevention measures are not entirely effective and are complicated by the patients' conditions, the multifactorial nature of the pathology, and an incomplete understanding of the etiology. Cellular technologies based on induced pluripotent stem cells (iPSCs) can provide a vast cellular resource for the production of artificial cartilage tissue for replacement therapy and allow the possibility of a personalized approach. However, the question remains whether a number of etiological abnormalities associated with joint disease are transmitted from the source cell to iPSCs and their chondrocyte derivatives. Some data state that there is no difference between the iPSCs and their derivatives from healthy and sick donors; however, there are other data indicating a dissimilarity. Therefore, this topic requires a thorough study of the differentiation potential of iPSCs and the factors influencing it, the risk factors associated with joint diseases, and a comparative analysis of the characteristics of cells obtained from patients. Together with cultivation optimization methods, these measures can increase the efficiency of obtaining cell technology products and make their wide practical application possible.

Matched MeSH terms: Cartilage, Articular*
The role of autophagy in mitigating osteoarthritis progression via regulation of chondrocyte apoptosis: A review

Kong P, Ahmad RE, Zulkifli A, Krishnan S, Nam HY, Kamarul T

Joint Bone Spine, 2024 May;91(3):105642.
PMID: 37739213 DOI: 10.1016/j.jbspin.2023.105642

Osteoarthritis (OA) is the most prevalent chronic joint disease with an immense socioeconomic burden; however, no treatment has achieved complete success in effectively halting or reversing cartilage degradation, which is the central pathophysiological feature of OA. Chondrocytes loss or dysfunction is a significant contributing factor to the progressive cartilage deterioration as these sole resident cells have a crucial role to produce extracellular matrix proteins, thus maintaining cartilage structure and homeostasis. It has been previously suggested that death of chondrocytes occurring through apoptosis substantially contributes to cartilage degeneration. Although the occurrence of apoptosis in osteoarthritic cartilage and its correlation with cartilage degradation is evident, the causes of chondrocyte apoptosis leading to matrix loss are still not well-understood. Autophagy, an intracellular degradative mechanism that eliminates dysfunctional cytoplasmic components to aid cell survival in unfavourable conditions, is a potential therapeutic target to inhibit chondrocyte apoptosis and reduce OA severity. Despite accumulating evidence indicating significant cytoprotective effects of autophagy against chondrocyte apoptosis, the mechanistic link between autophagy and apoptosis in chondrocytes remains to be further explored. In this review, we summarize the relevant mechanistic events that perpetuate chondrocyte apoptosis and highlight the prominent role of autophagy in modulating these events to mitigate OA progression.

Matched MeSH terms: Cartilage, Articular/pathology
Fulltext The crosstalk between mesenchymal stem cells and damaged cartilage in osteoarthritis

Satar Jabbar Rahi Algraittee, Rajesh Ramasamy

Malaysian Journal of Medicine and Health Sciences, 2020;16(2):262-268.
MyJurnal

Human cartilage contains multipotent stem cells, namely mesenchymal stem cells (MSCs) which are progenitors of connective tissue that play homeostatic and reparative roles. Although the major constituent cells in the cartilage are chondrocytes, they possess a limited regenerative ability, and as a result, spontaneous cartilage repair by chondro- cytes leads to the synthesis of fibrocartilage. Similarly, MSCs derived from articular cartilage of osteoarthritis patients have demonstrated inadequacy in cartilage repair. The role of MSCs in the pathophysiology of osteoarthritis (OA) is not entirely understood, whether the inflammatory milieu associated with OA joints affects the reparative properties of MSCs or the inherent defects of OA cartilage-derived MSCs impair the proper execution of the required immu- nosuppressive and reparative functions. Therefore, the current review explores the biological characteristics and features of MSCs derived from physiological state and OA condition with the aim of identifying how OA affects MSC functions as well as the role of MSCs in the pathophysiology of OA.

Matched MeSH terms: Cartilage, Articular
Scaffolds for Cartilage Regeneration: To Use or Not to Use?

Sha'ban M, Ahmad Radzi MA

Adv Exp Med Biol, 2020;1249:97-114.
PMID: 32602093 DOI: 10.1007/978-981-15-3258-0_7

Joint cartilage has been a significant focus on the field of tissue engineering and regenerative medicine (TERM) since its inception in the 1980s. Represented by only one cell type, cartilage has been a simple tissue that is thought to be straightforward to deal with. After three decades, engineering cartilage has proven to be anything but easy. With the demographic shift in the distribution of world population towards ageing, it is expected that there is a growing need for more effective options for joint restoration and repair. Despite the increasing understanding of the factors governing cartilage development, there is still a lot to do to bridge the gap from bench to bedside. Dedicated methods to regenerate reliable articular cartilage that would be equivalent to the original tissue are still lacking. The use of cells, scaffolds and signalling factors has always been central to the TERM. However, without denying the importance of cells and signalling factors, the question posed in this chapter is whether the answer would come from the methods to use or not to use scaffold for cartilage TERM. This paper presents some efforts in TERM area and proposes a solution that will transpire from the ongoing attempts to understand certain aspects of cartilage development, degeneration and regeneration. While an ideal formulation for cartilage regeneration has yet to be resolved, it is felt that scaffold is still needed for cartilage TERM for years to come.

Matched MeSH terms: Cartilage, Articular/physiology*
Protease activated receptor 2 and matriptase expression in the joints of cats with and without osteoarthritis

Ariffin SMZ, Bennett D, Ferrell WR, Lockhart JC, Dunning L, Clements DN, et al.

J Feline Med Surg, 2021 08;23(8):794-803.
PMID: 33284033 DOI: 10.1177/1098612X20977796

OBJECTIVES: The aim of this study was to determine the presence of protease-activated receptor 2 (PAR2) and matriptase proteins and quantify PAR2 and matriptase mRNA expression in the articular cartilage and synovial membrane of cats with and without osteoarthritis (OA).
METHODS: A total of 28 articular cartilage samples from adult cats (14 OA and 14 normal), 10 synovial membranes from adult cats (five OA and five normal) and three cartilage samples from 9-week-old fetal cats were used. The presence of PAR2 and matriptase in the cartilage and synovial membrane of the adult samples was detected by immunohistochemical (IHC) staining, while real-time PCR was used for mRNA expression analyses in all samples.
RESULTS: PAR2 was detected in all OA and normal articular cartilage and synovial membrane samples but confined to only a few superficial chondrocytes in the normal samples. Matriptase was only detected in OA articular cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression were, however, detected in all cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression levels in OA articular cartilage were five (P <0.001) and 3.3 (P <0.001) times higher than that of the healthy group, respectively. There was no significant difference (P = 0.05) in the OA synovial membrane PAR2 and matriptase mRNA expression compared with the normal samples.
CONCLUSIONS AND RELEVANCE: Detection of PAR2 and matriptase proteins and gene expression in feline articular tissues is a novel and important finding, and supports the hypothesis that serine proteases are involved in the pathogenesis of feline OA. The consistent presence of PAR2 and matriptase protein in the cytoplasm of OA chondrocytes suggests a possible involvement of proteases in cartilage degradation. Further investigations into the PAR2 and matriptase pathobiology could enhance our understanding of the proteolytic cascades in feline OA, which might lead to the development of novel therapeutic strategies.

Matched MeSH terms: Cartilage, Articular*
A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage

Kamarul T, Ab-Rahim S, Tumin M, Selvaratnam L, Ahmad TS

Eur Cell Mater, 2011 Mar 15;21:259-71; discussion 270-1.
PMID: 21409755

The effects of Glucosamine Sulphate (GS) and Chondroitin Sulphate (CS) on the healing of damaged and repaired articular cartilage were investigated. This study was conducted using 18 New Zealand white rabbits as experimental models. Focal cartilage defects, surgically created in the medial femoral condyle, were either treated by means of autologous chondrocyte implantation (ACI) or left untreated as controls. Rabbits were then divided into groups which received either GS+/-CS or no pharmacotherapy. Three rabbits from each group were sacrificed at 12 and 24 weeks post-surgery. Knees dissected from rabbits were then evaluated using gross quantification of repair tissue, glycosaminoglycan (GAG) assays, immunoassays and histological assessments. It was observed that, in contrast to untreated sites, surfaces of the ACI-repaired sites appeared smooth and continuous with the surrounding native cartilage. Histological examination demonstrated a typical hyaline cartilage structure; with proteoglycans, type II collagen and GAGs being highly expressed in repair areas. The improved regeneration of these repair sites was also noted to be significant over time (6 months vs. 3 months) and in GS and GS+CS groups compared to the untreated (without pharmacotherapy) group. Combination of ACI and pharmacotherapy (with glucosamine sulphate alone/ or with chondroitin sulphate) may prove beneficial for healing of damaged cartilage, particularly in relation to focal cartilage defects.

Matched MeSH terms: Cartilage, Articular/drug effects*; Cartilage, Articular/pathology; Cartilage, Articular/surgery*
Articular cartilage restoration in load-bearing osteochondral defects by implantation of autologous chondrocyte-fibrin constructs: an experimental study in sheep

Munirah S, Samsudin OC, Chen HC, Salmah SH, Aminuddin BS, Ruszymah BH

J Bone Joint Surg Br, 2007 Aug;89(8):1099-109.
PMID: 17785753

Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous 'chondrocyte-fibrin' construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis. All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O'Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage. Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI.

Matched MeSH terms: Cartilage, Articular/metabolism; Cartilage, Articular/physiology; Cartilage, Articular/surgery*
Fulltext Extracellular Vesicles in the Synovial Joint: Is there a Role in the Pathophysiology of Osteoarthritis?

Esa A, Connolly KD, Williams R, Archer CW

Malays Orthop J, 2019 Mar;13(1):1-7.
PMID: 31001376 DOI: 10.5704/MOJ.1903.012

The role of extracellular vesicles (EV) in osteoarthritis has become the focus of much research. These vesicles were isolated from several cell types found in synovial joint including chondrocytes and synovium. As articular cartilage is an avascular tissue surrounded by synovial fluid, it is believed that EV might play a crucial role in the homeostasis of cartilage and also could hold key information in the pathogenesis of osteoarthritis. This is thought to be due to activation of pro-inflammatory factors leading to a catabolic state and degradation of cartilage. In addition, due to the nature of articular cartilage lacking neuronal innervation, knowledge of EV can contribute to identification of novel biomarkers in this debilitating condition. This can be either directly isolated from aspirate of synovial fluid or from peripheral blood. Finally, EVs are known to shuttle important signalling molecules which can be utilised as unique modality in transferring therapeutic compounds in a cell free manner.

Matched MeSH terms: Cartilage, Articular
Fulltext Mesenchymal stromal cells for cartilage repair in osteoarthritis

Mamidi MK, Das AK, Zakaria Z, Bhonde R

Osteoarthritis Cartilage, 2016 Aug;24(8):1307-16.
PMID: 26973328 DOI: 10.1016/j.joca.2016.03.003

Treatment for articular cartilage damage is quite challenging as it shows limited repair and regeneration following injury. Non-operative and classical surgical techniques are inefficient in restoring normal anatomy and function of cartilage in osteoarthritis (OA). Thus, investigating new and effective strategies for OA are necessary to establish feasible therapeutic solutions. The emergence of the new discipline of regenerative medicine, having cell-based therapy as its primary focus, may enable us to achieve repair and restore the damaged articular cartilage. This review describes progress and development of employing mesenchymal stromal cell (MSC)-based therapy as a promising alternative for OA treatment. The objective of this review is to first, discuss how in vitro MSC chondrogenic differentiation mimics in vivo embryonic cartilage development, secondly, to describe various chondrogenic differentiation strategies followed by pre-clinical and clinical studies demonstrating their feasibility and efficacy. However, several challenges need to be tackled before this research can be translated to the clinics. In particular, better understanding of the post-transplanted cell behaviour and learning to enhance their potency in the disease microenvironment is essential. Final objective is to underscore the importance of isolation, storage, cell shipment, route of administration, optimum dosage and control batch to batch variations to realise the full potential of MSCs in OA clinical trials.

Matched MeSH terms: Cartilage, Articular
Extracellular matrix integrity affects the mechanical behaviour of in-situ chondrocytes under compression

Moo EK, Han SK, Federico S, Sibole SC, Jinha A, Abu Osman NA, et al.

J Biomech, 2014 Mar 21;47(5):1004-13.
PMID: 24480705 DOI: 10.1016/j.jbiomech.2014.01.003

Cartilage lesions change the microenvironment of cells and may accelerate cartilage degradation through catabolic responses from chondrocytes. In this study, we investigated the effects of structural integrity of the extracellular matrix (ECM) on chondrocytes by comparing the mechanics of cells surrounded by an intact ECM with cells close to a cartilage lesion using experimental and numerical methods. Experimentally, 15% nominal compression was applied to bovine cartilage tissues using a light-transmissible compression system. Target cells in the intact ECM and near lesions were imaged by dual-photon microscopy. Changes in cell morphology (N(cell)=32 for both ECM conditions) were quantified. A two-scale (tissue level and cell level) Finite Element (FE) model was also developed. A 15% nominal compression was applied to a non-linear, biphasic tissue model with the corresponding cell level models studied at different radial locations from the centre of the sample in the transient phase and at steady state. We studied the Green-Lagrange strains in the tissue and cells. Experimental and theoretical results indicated that cells near lesions deform less axially than chondrocytes in the intact ECM at steady state. However, cells near lesions experienced large tensile strains in the principal height direction, which are likely associated with non-uniform tissue radial bulging. Previous experiments showed that tensile strains of high magnitude cause an up-regulation of digestive enzyme gene expressions. Therefore, we propose that cartilage degradation near tissue lesions may be due to the large tensile strains in the principal height direction applied to cells, thus leading to an up-regulation of catabolic factors.

Matched MeSH terms: Cartilage, Articular/injuries*; Cartilage, Articular/physiology
Dual photon excitation microscopy and image threshold segmentation in live cell imaging during compression testing

Moo EK, Abusara Z, Abu Osman NA, Pingguan-Murphy B, Herzog W

J Biomech, 2013 Aug 9;46(12):2024-31.
PMID: 23849134 DOI: 10.1016/j.jbiomech.2013.06.007

Morphological studies of live connective tissue cells are imperative to helping understand cellular responses to mechanical stimuli. However, photobleaching is a constant problem to accurate and reliable live cell fluorescent imaging, and various image thresholding methods have been adopted to account for photobleaching effects. Previous studies showed that dual photon excitation (DPE) techniques are superior over conventional one photon excitation (OPE) confocal techniques in minimizing photobleaching. In this study, we investigated the effects of photobleaching resulting from OPE and DPE on morphology of in situ articular cartilage chondrocytes across repeat laser exposures. Additionally, we compared the effectiveness of three commonly-used image thresholding methods in accounting for photobleaching effects, with and without tissue loading through compression. In general, photobleaching leads to an apparent volume reduction for subsequent image scans. Performing seven consecutive scans of chondrocytes in unloaded cartilage, we found that the apparent cell volume loss caused by DPE microscopy is much smaller than that observed using OPE microscopy. Applying scan-specific image thresholds did not prevent the photobleaching-induced volume loss, and volume reductions were non-uniform over the seven repeat scans. During cartilage loading through compression, cell fluorescence increased and, depending on the thresholding method used, led to different volume changes. Therefore, different conclusions on cell volume changes may be drawn during tissue compression, depending on the image thresholding methods used. In conclusion, our findings confirm that photobleaching directly affects cell morphology measurements, and that DPE causes less photobleaching artifacts than OPE for uncompressed cells. When cells are compressed during tissue loading, a complicated interplay between photobleaching effects and compression-induced fluorescence increase may lead to interpretations in cell responses to mechanical stimuli that depend on the microscopic approach and the thresholding methods used and may result in contradictory interpretations.

Matched MeSH terms: Cartilage, Articular/cytology; Cartilage, Articular/metabolism*
Biomechanical characterisation of ovine spinal facet joint cartilage

Abd Latif MJ, Jin Z, Wilcox RK

J Biomech, 2012 May 11;45(8):1346-52.
PMID: 22483055 DOI: 10.1016/j.jbiomech.2012.03.015

The spinal facet joints are known to be an important component in the kinematics and the load transmission of the spine. The articular cartilage in the facet joint is prone to degenerative changes which lead to back pain and treatments for the condition have had limited long term success. There is currently a lack of information on the basic biomechanical properties of the facet joint cartilage which is needed to develop tissue substitution or regenerative interventions. In the present study, the thickness and biphasic properties of ovine facet cartilage were determined using a combination of indentation tests and computational modelling. The equilibrium biphasic Young's modulus and permeability were derived to be 0.76±0.35 MPa and 1.61±1.10×10⁻¹⁵ m⁴/(Ns) respectively, which were within the range of cartilage properties characterised from the human synovial joints. The average thickness of the ovine facet cartilage was 0.52±0.10 mm, which was measured using a needle indentation test. These properties could potentially be used for the development of substitution or tissue engineering interventions and for computational modelling of the facet joint. Furthermore, the developed method to characterise the facet cartilage could be used for other animals or human donors.

Matched MeSH terms: Cartilage, Articular/anatomy & histology; Cartilage, Articular/physiology*
In vitro development of autologous tissue engineered human articular neocartilage for orthopaedic surgery

Samsudin OC, Aminuddin BS, Munirah S, Chua KH, Fuzina NH, Isa MR, et al.

Med J Malaysia, 2004 May;59 Suppl B:15-6.
PMID: 15468796

Treatment of articular cartilage lesions remains a clinical challenge. The uses of prosthetic joint replace allograft and/or autograft transplant carry a risk of complications due to infection, loosening of its component, immunological rejection and morbidity at the donor site. There has been an increasing interest in the management of cartilage damages, owing to the introduction of new therapeutic options. Tissue engineering as a method for tissue restoration begins to provide a potential alternative therapy for autologous grafts transplantations. We aimed to evaluate how well a tissue engineered neocartilage implant, consist of human articular chondrocytes cultured with the presence of autologous serum and mixed in a fresh fibrin derived from patient, would perform in subcutaneous implantation in athymic mice.

Matched MeSH terms: Cartilage, Articular/injuries; Cartilage, Articular/physiology
Fulltext Ultrastructural changes of the articular cartilage in some arthropathies with special reference to chondrocyte cell death

Kapitonova MY, Mansor O

Malays J Pathol, 2003 Jun;25(1):15-27.
PMID: 16196374

OBJECTIVE: To determine in situ using TEM the balance of apoptosis and necrosis in the articular cartilage of patients with inflammatory (rheumatoid arthritis and seronegative spondyloarthritis) and degenerative (osteoarthritis) joint diseases and to establish possible correlation between the cell death rate and the matrix vesicles formation.
METHODS: Cartilage samples of the knee joint were obtained from patients with rheumatoid arthritis (RA, 18 cases), osteoarthritis (OA, 22 cases), Reiter's disease (RD, 9 cases), peripheral form of the ankylosing spondyloarthritis (AS, 6 cases) and psoriatic arthritis (PA, 6 cases) during arthroscopy or knee surgery. Normal samples taken from autopsy cases without a history of joint diseases were used as control. Samples were processed for TEM with subsequent semi-quantitative estimation of the cell death rate in the superficial, middle and deep zone of non-calcified articular cartilage, and computer-aided ultramorphometric evaluation of the matrix vesicles of different types.
RESULTS: Both apoptotic and necrotic cell death could be identified in the cartilage of patients with inflammatory joint diseases, including seronegative spondyloarthritides and degenerative arthropathies. Apoptosis dominated over necrosis in all examined arthritides, including RA patients in which necrosis of the chondrocyte was the most frequent among arthropathies, while the highest apoptotic cell death rate was discovered in OA in which it correlated with the volume and numeric density of the matrix vesicles. These data provide evidence that apoptosis may contribute to the cartilage breakdown not only in RA and OA but also in the seronegative spondyloarthritides, which had a significantly higher apoptotic rate than the normal cartilage.

Matched MeSH terms: Cartilage, Articular/pathology*; Cartilage, Articular/ultrastructure
Fulltext Genipin crosslinked chitosan/PEO nanofibrous scaffolds exhibiting an improved microenvironment for the regeneration of articular cartilage

Ching KY, Andriotis O, Sengers B, Stolz M

J Biomater Appl, 2021 09;36(3):503-516.
PMID: 33730922 DOI: 10.1177/08853282211002015

Towards optimizing the growth of extracellular matrix to produce repair cartilage for healing articular cartilage (AC) defects in joints, scaffold-based tissue engineering approaches have recently become a focus of clinical research. Scaffold-based approaches by electrospinning aim to support the differentiation of chondrocytes by providing an ultrastructure similar to the fibrillar meshwork in native cartilage. In a first step, we demonstrate how the blending of chitosan with poly(ethylene oxide) (PEO) allows concentrated chitosan solution to become electrospinnable. The chitosan-based scaffolds share the chemical structure and characteristics of glycosaminoglycans, which are important structural components of the cartilage extracellular matrix. Electrospinning produced nanofibrils of ∼100 nm thickness that are closely mimicking the size of collagen fibrils in human AC. The polymer scaffolds were stabilized in physiological conditions and their stiffness was tuned by introducing the biocompatible natural crosslinker genipin. We produced scaffolds that were crosslinked with 1.0% genipin to obtain values of stiffness that were in between the stiffness of the superficial zone human AC of 600 ± 150 kPa and deep zone AC of 1854 ± 483 kPa, whereas the stiffness of 1.5% genipin crosslinked scaffold was similar to the stiffness of deep zone AC. The scaffolds were degradable, which was indicated by changes in the fibril structure and a decrease in the scaffold stiffness after seven months. Histological and immunohistochemical analysis after three weeks of culture with human articular chondrocytes (HACs) showed a cell viability of over 90% on the scaffolds and new extracellular matrix deposited on the scaffolds.

Matched MeSH terms: Cartilage, Articular/cytology; Cartilage, Articular/physiology*

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