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Fulltext The Skeletal Effects of Tanshinones: A Review

Ekeuku SO, Pang KL, Chin KY

Molecules, 2021 Apr 16;26(8).
PMID: 33923673 DOI: 10.3390/molecules26082319

BACKGROUND: Osteoporosis results from excessive bone resorption and reduced bone formation, triggered by sex hormone deficiency, oxidative stress and inflammation. Tanshinones are a class of lipophilic phenanthrene compounds found in the roots of Salvia miltiorrhiza with antioxidant and anti-inflammatory activities, which contribute to its anti-osteoporosis effects. This systematic review aims to provide an overview of the skeletal beneficial effects of tanshinones.
METHODS: A systematic literature search was conducted in January 2021 using Pubmed, Scopus and Web of Science from the inception of these databases. Original studies reporting the effects of tanshinones on bone through cell cultures, animal models and human clinical trials were considered.
RESULTS: The literature search found 158 unique articles on this topic, but only 20 articles met the inclusion criteria and were included in this review. The available evidence showed that tanshinones promoted osteoblastogenesis and bone formation while reducing osteoclastogenesis and bone resorption.
CONCLUSIONS: Tanshinones modulates bone remodelling by inhibiting osteoclastogenesis and osteoblast apoptosis and stimulating osteoblastogenesis. Therefore, it might complement existing strategies to prevent bone loss.

Matched MeSH terms: Osteoblasts/drug effects
Low dose of tocotrienols protects osteoblasts against oxidative stress

Nizar AM, Nazrun AS, Norazlina M, Norliza M, Ima Nirwana S

Clin Ter, 2011;162(6):533-8.
PMID: 22262323

Vitamin E is an antioxidant that may protect bone against oxidative stress-induced osteoporosis. This in vitro study was conducted to determine the protective effects of a-tocopherol and γ-tocotrienol on osteoblasts, the bone forming cells, against oxidative stress.

Matched MeSH terms: Osteoblasts/drug effects*
In vitro cytotoxicity evaluation of biomaterials on human osteoblast cells CRL-1543; hydroxyapatite, natural coral and polyhydroxybutarate

Shamsuria O, Fadilah AS, Asiah AB, Rodiah MR, Suzina AH, Samsudin AR

Med J Malaysia, 2004 May;59 Suppl B:174-5.
PMID: 15468874

The aim of this study was to evaluate the in vitro cytotoxicity of biomaterials; Hydroxyapatite (HA), Natural coral (NC) and Polyhydroxybutarate (PHB). Three different materials used in this study; HA (Ca10(PO4)6(OH)2), NC (CaCO3) and PHB (Polymer) were locally produced by the groups of researcher from Universiti Sains Malaysia. The materials were separately extracted in the complete culture medium (100mg/ml) for 72h and introduced to the osteoblast cells CRL-1543. The viability of osteoblast CRL-1543 cultivated with these extraction materials after 72h incubation period was compared to negative control with neutral red assay by using spectrophotometer at 540nm. The results showed the non-cytotoxicity of the materials. After 72h of incubation period, HA showed 123% viable cells, NC was 99.43% and PHB was 176.75%. In this study, cytotoxicity test dealt mainly with the substances that leached out from the biomaterial. The results obtained showed that the materials were not toxic and also promoted cells growth in the sense of biofunctionality.

Matched MeSH terms: Osteoblasts/drug effects*
In vitro degradation and cell viability assessment of Zn-3Mg alloy for biodegradable bone implants

Dambatta MS, Murni NS, Izman S, Kurniawan D, Froemming GR, Hermawan H

Proc Inst Mech Eng H, 2015 May;229(5):335-42.
PMID: 25991712 DOI: 10.1177/0954411915584962

This article reports the in vitro degradation and cytotoxicity assessment of Zn-3Mg alloy developed for biodegradable bone implants. The alloy was prepared using casting, and its microstructure was composed of Mg2Zn11 intermetallic phase distributed within a Zn-rich matrix. The degradation assessment was done using potentiodynamic polarization and electrochemical impedance spectrometry. The cell viability and the function of normal human osteoblast cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and alkaline phosphatase extracellular enzyme activity assays. The results showed that the degradation rate of the alloy was slower than those of pure Zn and pure Mg due to the formation of a high polarization resistance oxide film. The alloy was cytocompatible with the normal human osteoblast cells at low concentrations (<0.5 mg/mL), and its alkaline phosphatase activity was superior to pure Mg. This assessment suggests that Zn-3Mg alloy has the potential to be developed as a material for biodegradable bone implants, but the toxicity limit must be carefully observed.

Matched MeSH terms: Osteoblasts/drug effects
Mixed-ligand copper(II) complex of quercetin regulate osteogenesis and angiogenesis

Vimalraj S, Rajalakshmi S, Raj Preeth D, Vinoth Kumar S, Deepak T, Gopinath V, et al.

Mater Sci Eng C Mater Biol Appl, 2018 Feb 01;83:187-194.
PMID: 29208278 DOI: 10.1016/j.msec.2017.09.005

Copper(II) complex of quercetin Cu+Q, mixed ligand complexes, quercetin-Cu(II)-phenanthroline [Cu+Q(PHt)] and quercetin-Cu(II)-neocuproine [Cu+Q(Neo)] have been synthesized and characterized. From the FT-IR spectroscopic studies, it was evident that C-ring of quercetin is involved in the metal chelation in all the three copper complexes. C-ring chelation was further proven by UV-Visible spectra and the presence of Cu(II) from EPR spectroscopic investigations. These complexes were found to have osteogenic and angiogenic properties, observed through in vitro osteoblast differentiation and chick embryo angiogenesis assay. In osteoblast differentiation, quercetin-Cu(II) complexes treatment increased calcium deposition and alkaline phosphatase activity (ALP) activity at the cellular level and stimulated Runx2 mRNA and protein, ALP mRNA and type 1 collagen mRNA expression at the molecular level. Among the complexes, Q+Cu(PHt) showed more effects on osteoblast differentiation when compared to that of other two copper complexes. Additionally, Q+Cu(Neo) showed more effect compared to Q+Cu. Furthermore, the effect of these complexes on osteoblast differentiation was confirmed by the expression of osteoblast specific microRNA, pre-mir-15b. The chick embryo angiogenesis assay showed that angiogenic parameters such as blood vessel length, size and junctions were stimulated by these complexes. Thus, the present study demonstrated that quercetin copper(II) complexes exhibit as a pharmacological agent for the orthopedic application.

Matched MeSH terms: Osteoblasts/drug effects
Fulltext Application of Propolis in Protecting Skeletal and Periodontal Health-A Systematic Review

Ekeuku SO, Chin KY

Molecules, 2021 May 25;26(11).
PMID: 34070497 DOI: 10.3390/molecules26113156

Chronic inflammation and oxidative stress are two major mechanisms leading to the imbalance between bone resorption and bone formation rate, and subsequently, bone loss. Thus, functional foods and dietary compounds with antioxidant and anti-inflammatory could protect skeletal health. This review aims to examine the current evidence on the skeletal protective effects of propolis, a resin produced by bees, known to possess antioxidant and anti-inflammatory activities. A literature search was performed using Pubmed, Scopus, and Web of Science to identify studies on the effects of propolis on bone health. The search string used was (i) propolis AND (ii) (bone OR osteoporosis OR osteoblasts OR osteoclasts OR osteocytes). Eighteen studies were included in the current review. The available experimental studies demonstrated that propolis could prevent bone loss due to periodontitis, dental implantitis, and diabetes in animals. Combined with synthetic and natural grafts, it could also promote fracture healing. Propolis protects bone health by inhibiting osteoclastogenesis and promoting osteoblastogenesis, partly through its antioxidant and anti-inflammatory actions. Despite the promising preclinical results, the skeletal protective effects of propolis are yet to be proven in human studies. This research gap should be bridged before nutraceuticals based on propolis with specific health claims can be developed.

Matched MeSH terms: Osteoblasts/drug effects
Fulltext Protective Effects of Selected Botanical Agents on Bone

Jolly JJ, Chin KY, Alias E, Chua KH, Soelaiman IN

Int J Environ Res Public Health, 2018 05 11;15(5).
PMID: 29751644 DOI: 10.3390/ijerph15050963

Osteoporosis is a serious health problem affecting more than 200 million elderly people worldwide. The early symptoms of this disease are hardly detectable. It causes progressive bone loss, which ultimately renders the patients susceptible to fractures. Osteoporosis must be prevented because the associated fragility fractures result in high morbidity, mortality, and healthcare costs. Many plants used in herbal medicine contain bioactive compounds possessing skeletal protective effects. This paper explores the anti-osteoporotic properties of selected herbal plants, including their actions on osteoblasts (bone forming cells), osteoclasts (bone resorbing cells), and bone remodelling. Some of the herbal plant families included in this review are Berberidaceae, Fabaceae, Arecaceae, Labiatae, Simaroubaceaea, and Myrsinaceae. Their active constituents, mechanisms of action, and pharmaceutical applications were discussed. The literature shows that very few herbal plants have undergone human clinical trials to evaluate their pharmacological effects on bone to date. Therefore, more intensive research should be performed on these plants to validate their anti-osteoporotic properties so that they can complement the currently available conventional drugs in the battle against osteoporosis.

Matched MeSH terms: Osteoblasts/drug effects
Partial oxidation of TiN coating by hydrothermal treatment and ozone treatment to improve its osteoconductivity

Shi X, Xu L, Le TB, Zhou G, Zheng C, Tsuru K, et al.

Mater Sci Eng C Mater Biol Appl, 2016 Feb;59:542-548.
PMID: 26652406 DOI: 10.1016/j.msec.2015.10.024

Dental implants made of pure titanium suffer from abrasion and scratch during routine oral hygiene procedures. This results in an irreversible surface damage, facilitates bacteria adhesion and increases risk of peri-implantitis. To overcome these problems, titanium nitride (TiN) coating was introduced to increase surface hardness of pure titanium. However, the osteoconductivity of TiN is considered to be similar or superior to that of titanium and its alloys and therefore surface modification is necessary. In this study, TiN coating prepared through gas nitriding was partially oxidized by hydrothermal (HT) treatment and ozone (O3) treatment in pure water to improve its osteoconductivity. The effects of HT treatment and O3 treatment on surface properties of TiN were investigated and the osteoconductivity after undergoing treatment was assessed in vitro using osteoblast evaluation. The results showed that the critical temperature for HT treatment was 100°C since higher temperatures would impair the hardness of TiN coating. By contrast, O3 treatment was more effective in oxidizing TiN surfaces, improving its wettability while preserving its morphology and hardness. Osteoblast attachment, proliferation, alkaline phosphatase (ALP) expression and mineralization were improved on oxidized specimens, especially on O3 treated specimens, compared with untreated ones. These effects seemed to be consequences of partial oxidation, as well as improved hydrophilicity and surface decontamination. Finally, it was concluded that, partially oxidized TiN is a promising coating to be used for dental implant.

Matched MeSH terms: Osteoblasts/drug effects*
Characterization of nickel-doped biphasic calcium phosphate/graphene nanoplatelet composites for biomedical application

Baradaran S, Moghaddam E, Nasiri-Tabrizi B, Basirun WJ, Mehrali M, Sookhakian M, et al.

Mater Sci Eng C Mater Biol Appl, 2015 Apr;49:656-668.
PMID: 25686995 DOI: 10.1016/j.msec.2015.01.050

The effect of the addition of an ionic dopant to calcium phosphates for biomedical applications requires specific research due to the essential roles played in such processes. In the present study, the mechanical and biological properties of Ni-doped hydroxyapatite (HA) and Ni-doped HA mixed with graphene nanoplatelets (GNPs) were evaluated. Ni (3wt.% and 6wt.%)-doped HA was synthesized using a continuous precipitation method and calcined at 900°C for 1h. The GNP (0.5-2wt.%)-reinforced 6% Ni-doped HA (Ni6) composite was prepared using rotary ball milling for 15h. The sintering process was performed using hot isostatic pressing at processing conditions of 1150°C and 160MPa with a 1-h holding time. The results indicated that the phase compositions and structural features of the products were noticeably affected by the Ni and GNPs. The mechanical properties of Ni6 and 1.5Ni6 were increased by 55% and 75% in hardness, 59% and 163% in fracture toughness and 120% and 85% in elastic modulus compared with monolithic HA, respectively. The in-vitro biological behavior was investigated using h-FOB osteoblast cells in 1, 3 and 5days of culture. Based on the osteoblast results, the cytotoxicity of the products was indeed affected by the Ni doping. In addition, the effect of GNPs on the growth and proliferation of osteoblast cells was investigated in Ni6 composites containing different ratios of GNPs, where 1.5wt.% was the optimum value.

Matched MeSH terms: Osteoblasts/drug effects
Ascorbic acid induces osteoblast differentiation of human suspension mononuclear cells

Hadzir SN, Ibrahim SN, Abdul Wahab RM, Zainol Abidin IZ, Senafi S, Ariffin ZZ, et al.

Cytotherapy, 2014 May;16(5):674-82.
PMID: 24176546 DOI: 10.1016/j.jcyt.2013.07.013

Suspension mononuclear cells (MNCs) can be differentiated into osteoblasts with the induction of ascorbic acid and β-glycerophosphate. The aim of this study was to determine the ability of suspension MNCs to differentiate into osteoblasts using ascorbic acid only.

Matched MeSH terms: Osteoblasts/drug effects
The effect of nitric oxide on the production of prostaglandin E2 by hydroxyapatite-stimulated a human osteoblast (HOS) cell line

Sugiatno E, Samsudin AR, Ibrahim MF, Sosroseno W

Biomed Pharmacother, 2006 May;60(4):147-51.
PMID: 16581222

The aim of the present study was to determine the effect of nitric oxide (NO) on the production of prostaglandin E2 (PGE2) by a human osteoblast cell line (HOS cells) stimulated with hydroxyapatite. Cells were cultured on the HA surfaces with or without the presence of NO donors (SNAP and NAP) for 3 days. The effect of NO scavenger, carboxy PTIO, or endothelial nitric oxide synthase (eNOS) inhibitor, L-NIO, was assessed by adding this scavenger in the cultures of HA-stimulated HOS cells with or without the presence of SNAP. Furthermore, HOS cells were pre-treated with anti-human integrin alphaV antibody, indomethacin, a non-specific inhibitor, aspirin, a COX-1 inhibitor, or nimesulide, a COX-2 inhibitor, prior to culturing on HA surfaces with or without the presence of SNAP. The levels of PGE2 were determined from the 3 day culture supernatants. The results showed that the production of PGE2 by HA-stimulated HOS cells was augmented by SNAP. Carboxy PTIO suppressed but L-NIO only partially inhibited the production of PGE2 by HA-stimulated HOS cells with or without the presence of exogenous NO. Pre-treatment of the cells with anti-human integrin alphaV antibody, indomethacin or nimesulide but not aspirin suppressed the production of PGE2 by HA-stimulated HOS cells with or without the presence of NO. Therefore, the results of the present study suggest that NO may up-regulate the production of PGE2 by augmenting the COX-2 pathway initiated by the binding between HOS cell-derived integrin alphaV and HA surface.

Matched MeSH terms: Osteoblasts/drug effects*
In vitro differences of hydroxyapatite from different resources in simulated body fluid

Hashim N, Sabudin S, Ibrahim S, Zin NM, Bakar SH, Fazan F

Med J Malaysia, 2004 May;59 Suppl B:103-4.
PMID: 15468839

Hydroxyapatite (HA; Ca10(PO4)6(OH)2), is one of the significant implant materials used in Orthopaedics and Dental applications. However, synthetically produced HA may not be stable under ionic environment, which it will unavoidably encounter during its applications. In this paper, the in vitro effects of three HA materials derived from different resources, i.e. commercial HA (HAC), synthesised HA from pure chemicals (HAS) and synthesised HA from kapur sireh; derived traditionally from natural limestone (HAK), were studied. The HA disc samples were prepared and immersed in simulated body fluid (SBF) for 31-day period. The evaluation conducted focuses on the changes of the pH and the Calcium ion (Ca-ion) and Phosphate ion (P-ion) concentrations in the SBF solution, as well as the XRD and SEM data representing the reactions on the HA materials. From the XRD, it was found that HAK has the smallest crystallite sizes, which in turn affect the pH of the SBF during immersion. The Ca and P-ion concentrations generally decrease over time at different rates for different HA. Upon 1-day immersion in SBF, apatite growth was observed onto all three surfaces, which became more pronounced after 3-day immersion. However, the appetites formed were observed to be different in shapes and sizes. The reasons for the difference in the apatite-crystals and their subsequent effects on cells are still being investigated.

Matched MeSH terms: Osteoblasts/drug effects*
Employing different types of phytoestrogens improve bone mineralization in bisphenol A stimulated osteoblast

Thent ZC, Froemming GRA, Ismail ABM, Fuad SBSA, Muid S

Life Sci, 2018 Oct 01;210:214-223.
PMID: 30145154 DOI: 10.1016/j.lfs.2018.08.057

AIMS: Phytoestrogens and xenoestrogens act as agonists/antagonists in bone formation and differentiation. Strong bones are depending of the ability of osteoblasts to form new tissue and to mineralize the newly formed tissue. Dysfunctional or loss of mineralization leads to weak bone and increased fracture risk. In this study, we reported the effect of different types of phytoestrogens (daidzein, genistein and equol) on mineralization in hFOB 1.19 cells stimulated with bisphenol A (BPA).
MAIN METHODS: Cell mineralization capacity of phytoestrogens was investigated by evaluating calcium, phosphate content and alkaline phosphatase activity. Bone related markers, osteocalcin and osteonectin, responsible in maintaining mineralization were also measured.
KEY FINDINGS: BPA is significantly interfering with bone mineralization in hFOB 1.19 cells. However, the enhanced mineralization efficacy of daidzein and genistein (particularly at a dose of 5 and 40 μg/mL, respectively) was evidenced by increasing calcium and phosphate content, higher ALP activity, compared to the untreated BPA group. The quantitative analyses were confirmed through morphological findings. Osteocalcin and osteonectin levels were increased in phytoestrogens-treated cells. These findings revealed the potential effect of phytoestrogens in reverting the demineralization process due to BPA exposure in hFOB 1.19 cells.
SIGNIFICANCE: We found that osteoblast differentiation and mineralization were maintained following treatment with phytoestrogens under BPA exposure.

Matched MeSH terms: Osteoblasts/drug effects
Fulltext The Molecular Mechanism of Vitamin E as a Bone-Protecting Agent: A Review on Current Evidence

Wong SK, Mohamad NV, Ibrahim N', Chin KY, Shuid AN, Ima-Nirwana S

Int J Mol Sci, 2019 Mar 22;20(6).
PMID: 30909398 DOI: 10.3390/ijms20061453

Bone remodelling is a tightly-coordinated and lifelong process of replacing old damaged bone with newly-synthesized healthy bone. In the bone remodelling cycle, bone resorption is coupled with bone formation to maintain the bone volume and microarchitecture. This process is a result of communication between bone cells (osteoclasts, osteoblasts, and osteocytes) with paracrine and endocrine regulators, such as cytokines, reactive oxygen species, growth factors, and hormones. The essential signalling pathways responsible for osteoclastic bone resorption and osteoblastic bone formation include the receptor activator of nuclear factor kappa-B (RANK)/receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG), Wnt/β-catenin, and oxidative stress signalling. The imbalance between bone formation and degradation, in favour of resorption, leads to the occurrence of osteoporosis. Intriguingly, vitamin E has been extensively reported for its anti-osteoporotic properties using various male and female animal models. Thus, understanding the underlying cellular and molecular mechanisms contributing to the skeletal action of vitamin E is vital to promote its use as a potential bone-protecting agent. This review aims to summarize the current evidence elucidating the molecular actions of vitamin E in regulating the bone remodelling cycle.

Matched MeSH terms: Osteoblasts/drug effects
Fulltext The Effects of Quassinoid-Rich Eurycoma longifolia Extract on Bone Turnover and Histomorphometry Indices in the Androgen-Deficient Osteoporosis Rat Model

Jayusman PA, Mohamed IN, Alias E, Mohamed N, Shuid AN

Nutrients, 2018 Jun 21;10(7).
PMID: 29933617 DOI: 10.3390/nu10070799

Male osteoporosis is associated with higher rates of disability and mortality. Hence the search for suitable intervention and treatment to prevent the degeneration of skeletal health in men is necessary. Eurycoma longifolia (EL), a traditional plant with aphrodisiac potential may be used to treat and prevent male osteoporosis. The skeletal protective effect of quassinoid-rich EL extract, which has a high content of eurycomanone, has not been studied. This study aimed to determine whether EL could prevent skeletal deteriorations in gonadal hormone-deficient male rats. Ninety-six male Sprague⁻Dawley rats were randomly assigned to baseline, sham-operated (Sham), orchidectomised or chemically castrated groups. Chemical castration was achieved via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomised and degarelix-castrated rats were then divided into negative control groups (ORX, DGX), testosterone-treated groups (intramuscular injection at 7 mg/kg weekly) (ORX + TES, DGX + TES), and EL-supplemented groups receiving daily oral gavages at doses of 25 mg/kg (ORX + EL25, DGX + EL25), 50 mg/kg (ORX + EL50, DGX + EL50), and 100 mg/kg (ORX + EL100, DGX + EL100). Following 10 weeks of treatment, the rats were euthanized and their blood and femora were collected. Bone biochemical markers, serum testosterone, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa β-ligand (RANKL) levels and histomorphometric indices were evaluated. Quassinoid-rich EL supplementation was found to reduce degenerative changes of trabecular structure by improving bone volume, trabecular number, and separation. A reduction in the percentage of osteoclast and increase in percentage of osteoblast on bone surface were also seen with EL supplementation. Dynamic histomorphometric analysis showed that the single-labeled surface was significantly decreased while the double-labeled surface was significantly increased with EL supplementations. There was a marginal but significant increase in serum testosterone levels in the ORX + EL25, DGX + EL50, and DGX + EL100 groups compared to their negative control groups. Quassinoid-rich EL extract was effective in reducing skeletal deteriorations in the androgen-deficient osteoporosis rat model.

Matched MeSH terms: Osteoblasts/drug effects
Can soy prevent male osteoporosis? A review of the current evidence

Chin KY, Ima-Nirwana S

Curr Drug Targets, 2013 Dec;14(14):1632-41.
PMID: 24354587

The Asian population whose soy intake is higher compared to Western populations shows a significantly lower incidence of osteoporotic fracture. Several meta-analyses have revealed that supplementation of soy isoflavones improve bone health status in women. This review examined the current evidence as to whether soy could exhibit similar bone protective effects on the male population. In vivo studies revealed that supplementation of soy protein or soy isoflavones improved bone health in both normal and osteoporotic male rodents. Cell culture studies showed that soy isoflavones influenced osteogenesis and osteoclastogenesis through mechanisms such as estrogen receptor binding activity, antiinflammatory activity and anti-parathyroid hormone activity. Soy isoflavones also affected calcium channel signaling and might exhibit direct effects on the osteoblastogenesis modulator, core binding factor 1. However, limited clinical trials involving soy intervention in males generally showed insignificant results. This could be attributed to the short duration of intervention, characteristics of the subjects or method of bone health assessment. More well-planned clinical trials are required to establish possible bone protective effects of soy in men.

Matched MeSH terms: Osteoblasts/drug effects
A review of the possible mechanisms of action of tocotrienol - a potential antiosteoporotic agent

Chin KY, Mo H, Soelaiman IN

Curr Drug Targets, 2013 Dec;14(13):1533-41.
PMID: 23859472

Osteoporosis is posing a tremendous healthcare problem globally. Much effort has been invested in finding novel antiosteoporotic agents to stop the progression of this disease. Tocotrienol, one of the isoforms of vitamin E, is poised as a potential antiosteoporotic agent. Previous studies showed that tocotrienol as a single isomer or as a mixture demonstrated both anabolic and antiresorptive effects in various rodent models of osteoporosis. In vitro experiments further demonstrated that tocotrienol could up-regulate genes related to osteoblastogenesis and modify receptor activator of nuclear factor kappa B signaling against osteoclastogenesis. Additionally, tocotrienol was also shown to be a strong 3- hydroxy-3-methyl-glutaryl-CoA reductase down-regulator with a mechanism different from that of statins. Inhibition of the mevalonate pathway affects both osteoblast and osteoclast formation in favor of the former. Tocopherol, a more commonly used isoform of vitamin E does not possess similar effects. Tocotrienol is also a potent antioxidant. It can scavenge free radicals and prevent oxidative damage on osteoblast thus promoting its survival. It may also up-regulate the antioxidant defense network in osteoclast and indirectly act against free radical signaling essential in osteoclastogenesis. The effects of tocotrienol on Wnt/β-catenin signaling essential in osteoblastogenesis have not been determined. More mechanistic studies need to be conducted to illustrate the antiosteoporotic effects of tocotrienol. Clinical trials are also required to confirm its effects in humans. In conclusion, tocotrienol demonstrates great potential as an antiosteoporotic agent and much research effort should be invested to develop it as an agent to curb osteoporosis.

Matched MeSH terms: Osteoblasts/drug effects
Effects of fluoride-modified titanium surfaces on osteoblast proliferation and gene expression

Isa ZM, Schneider GB, Zaharias R, Seabold D, Stanford CM

Int J Oral Maxillofac Implants, 2006 Mar-Apr;21(2):203-11.
PMID: 16634490

PURPOSE: The objective of this study was to test the hypothesis that fluoride-modified titanium surfaces would enhance osteoblast differentiation. Osteoblast growth on a moderately rough etched fluoride-modified titanium surface (alteration in cellular differentiation) was compared to osteoblast growth on the same surface grit-blasted with titanium dioxide. The potential role of nanometer-level alterations on cell shape and subsequent differentiation was then compared.
MATERIALS AND METHODS: Human embryonic palatal mesenchymal (HEPM) cultures were incubated on the respective surfaces for 1, 3, and 7 days, followed by analysis for cell proliferation, alkaline phosphatase (ALP) -specific activity, and mRNA steady-state expression for bone-related genes (ALP, type I collagen, osteocalcin, bone sialoprotein [BSP] II, Cbfa1, and osterix) by real-time polymerase chain reaction (PCR).
RESULTS: The different surfaces did not alter the mRNA expression for ALP, type I collagen, osterix, osteocalcin, or BSP II. However, Cbfa1 expression on the fluoride-modified titanium surface was significantly higher (P < .001) at 1 week. The number of cells on this surface was 20% lower than the number of cells on the surface TiO2-blasted with 25-microm particles but not significantly different from the number of cells on the surface TiO2-blasted with 125-microm particles. Cells grown on all the titanium surfaces expressed similar levels of ALP activity.
CONCLUSIONS: The results indicated that a fluoride-modified surface topography, in synergy with surface roughness, may have a greater influence on the level of expression of Cbfa1 (a key regulator for osteogenesis) than the unmodified titanium surfaces studied.

Matched MeSH terms: Osteoblasts/drug effects*
Vitamin C and Bone Health: Evidence from Cell, Animal and Human Studies

Chin KY, Ima-Nirwana S

Curr Drug Targets, 2018;19(5):439-450.
PMID: 26343111 DOI: 10.2174/1389450116666150907100838

BACKGROUND: Vitamin C, traditionally associated with scurvy, is an important nutrient for maintaining bone health. It is essential in the production of collagen in bone matrix. It also scavenges free radicals detrimental to bone health.
OBJECTIVE: This review aims to assess the current evidence of the bone-sparing effects of vitamin C derived from cell, animal and human studies.
RESULTS: Cell studies showed that vitamin C was able to induce osteoblast and osteoclast formation. However, high-dose vitamin C might increase oxidative stress and subsequently lead to cell death. Vitamin C-deficient animals showed impaired bone health due to increased osteoclast formation and decreased bone formation. Vitamin C supplementation was able to prevent bone loss in several animal models of bone loss. Human studies generally showed a positive relationship between vitamin C and bone health, indicated by bone mineral density, fracture probability and bone turnover markers. Some studies suggested that the relationship between vitamin C and bone health could be U-shaped, more prominent in certain subgroups and different between dietary and supplemental form. However, most of the studies were observational, thus could not confirm causality. One clinical trial was performed, but it was not a randomized controlled trial, thus confounding factors could not be excluded.
CONCLUSION: vitamin C may exert beneficial effects on bone, but more rigorous studies and clinical trials should be performed to validate this claim.

Matched MeSH terms: Osteoblasts/drug effects
Evaluation of Tualang honey as a supplement to fetal bovine serum in cell culture

Kannan TP, Ali AQ, Abdullah SF, Ahmad A

Food Chem Toxicol, 2009 Jul;47(7):1696-702.
PMID: 19394390 DOI: 10.1016/j.fct.2009.04.020

The aim of this study was to evaluate Tualang honey as a supplement to fetal bovine serum in cell cultures using MTT assay, chromosome aberration test and gene expression analyses. The MTT assay showed the highest percentage of cell proliferation (105.3% increment than control) of human osteoblast cell line (CRL 1543) in 0.0195% honey in Dulbecco's modified eagle medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. There was enhanced cell proliferation corresponding to the decrease in concentrations of honey as indicated by the mitotic index values when the osteoblast cell line was incubated at 37 degrees C for 48 hours. There were no chromosome aberrations both in the honey treated as well as distilled water treated (negative control) cell lines. In the case of gene expression analyses, fibroblast cell lines (CCL 171) were treated with honey (0.0195%) for 24 and 48 hours separately. Though there was over expression for the bcl-xl gene at both 24 and 48 hours, under expression for bcl-xs gene at 24 hours and over expression at 48 hours and under expression for both c-myc and p53 genes at both 24 and 48 hours, none of them were statistically significant in altering the expression of mRNA.

Matched MeSH terms: Osteoblasts/drug effects

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