Displaying publications 1 - 20 of 43 in total

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  1. Zhang H, Zhao R, Wang X, Qi Y, Sandai D, Wang W, et al.
    Front Endocrinol (Lausanne), 2025;16:1488489.
    PMID: 39963284 DOI: 10.3389/fendo.2025.1488489
    Mitochondria maintain bacterial traits because of their endosymbiotic origins, yet the host cell recognizes them as non-threatening since the organelles are compartmentalized. Nevertheless, the controlled release of mitochondrial components into the cytoplasm can initiate cell death, activate innate immunity, and provoke inflammation. This selective interruption of endosymbiosis as early as 2 billion years ago allowed mitochondria to become intracellular signaling hubs. Recent studies have found that the interruption of mitochondrial symbiosis may be closely related to the occurrence of various diseases, especially osteoporosis (OP). OP is a systemic bone disease characterized by reduced bone mass, impaired bone microstructure, elevated bone fragility, and susceptibility to fracture. The interruption of intra-mitochondrial symbiosis affects the energy metabolism of bone cells, leads to the imbalance of bone formation and bone absorption, and promotes the occurrence of osteoporosis. In this paper, we reviewed the mechanism of mitochondrial intersymbiosis interruption in OP, discussed the relationship between mitochondrial intersymbiosis interruption and bone marrow mesenchymal stem cells, osteoblasts and osteoclasts, as well as the inheritance and adaptation in the evolutionary process, and prospected the future research direction to provide new ideas for clinical treatment.
    Matched MeSH terms: Osteoclasts/metabolism
  2. Mehat MZ, Shuid AN, Mohamed N, Muhammad N, Soelaiman IN
    J Bone Miner Metab, 2010 Sep;28(5):503-9.
    PMID: 20145960 DOI: 10.1007/s00774-010-0159-2
    Bone is a specialized connective tissue that functions as the load-bearing structure of the body. Free radicals may affect bone remodeling by regulating osteoclast activity in either the physiological or pathological condition. Vitamin E, a lipid-soluble antioxidant, has been demonstrated to offer protection against osteoporosis and to improve the bone material and structure of animal models. The aim of this study was to observe and compare the effects of alpha-tocopherol (alpha-tocopherol), delta-tocotrienol (delta-tocotrienol), and gamma-tocotrienol (gamma-tocotrienol) on the static and dynamic bone histomorphometric parameters in normal male rats. Thirty-two normal Sprague-Dawley male rats aged 3 months and weighing 200-250 g were randomly divided into four groups. The control group was supplemented with oral gavages of olive oil (vehicle), whereas the alpha-tocopherol, delta-tocotrienol, and gamma-tocotrienol groups were given oral gavages of 60 mg/kg alpha-tocopherol, delta-tocotrienol, and gamma-tocotrienol, respectively. The rats were injected twice with calcein to fluorochrome-label the bones. After 4 months of treatment, the rats were killed, and the left femurs were dissected out and prepared for bone histomorphometry. Both the static and dynamic parameters of the vitamin E-treated groups were better than those of the normal control group. Among the vitamin E-treated groups, the tocotrienol groups showed better histomorphometry results compared to the α-tocopherol group, with the γ-tocotrienol group demonstrating the best effects on both sets of parameters. We concluded that vitamin E can promote bone formation in normal rats, with gamma-tocotrienol being the most potent form of vitamin E.
    Matched MeSH terms: Osteoclasts/cytology; Osteoclasts/metabolism
  3. Zainal Ariffin SH, Lim KW, Megat Abdul Wahab R, Zainal Ariffin Z, Rus Din RD, Shahidan MA, et al.
    PeerJ, 2022;10:e14174.
    PMID: 36275474 DOI: 10.7717/peerj.14174
    BACKGROUND: There have been promising results published regarding the potential of stem cells in regenerative medicine. However, the vast variety of choices of techniques and the lack of a standard approach to analyse human osteoblast and osteoclast differentiation may reduce the utility of stem cells as a tool in medical applications. Therefore, this review aims to systematically evaluate the findings based on stem cell differentiation to define a standard gene expression profile approach.

    METHODS: This review was performed following the PRISMA guidelines. A systematic search of the study was conducted by retrieving articles from the electronic databases PubMed and Web of Science to identify articles focussed on gene expression and approaches for osteoblast and osteoclast differentiation.

    RESULTS: Six articles were included in this review; there were original articles of in vitro human stem cell differentiation into osteoblasts and osteoclasts that involved gene expression profiling. Quantitative polymerase chain reaction (qPCR) was the most used technique for gene expression to detect differentiated human osteoblasts and osteoclasts. A total of 16 genes were found to be related to differentiating osteoblast and osteoclast differentiation.

    CONCLUSION: Qualitative information of gene expression provided by qPCR could become a standard technique to analyse the differentiation of human stem cells into osteoblasts and osteoclasts rather than evaluating relative gene expression. RUNX2 and CTSK could be applied to detect osteoblasts and osteoclasts, respectively, while RANKL could be applied to detect both osteoblasts and osteoclasts. This review provides future researchers with a central source of relevant information on the vast variety of gene expression approaches in analysing the differentiation of human osteoblast and osteoclast cells. In addition, these findings should enable researchers to conduct accurately and efficiently studies involving isolated human stem cell differentiation into osteoblasts and osteoclasts.

    Matched MeSH terms: Osteoclasts*
  4. Ariffin SH, Abidin IZ, Yazid MD, Wahab RM
    Cell Commun Signal, 2010;8:29.
    PMID: 20969794 DOI: 10.1186/1478-811X-8-29
    The purpose of this study is to determine whether isolated suspension mouse peripheral mononucleated blood cells have the potential to differentiate into two distinct types of cells, i.e., osteoblasts and osteoclasts.
    Matched MeSH terms: Osteoclasts
  5. Chin KY
    Int J Med Sci, 2018;15(12):1373-1383.
    PMID: 30275766 DOI: 10.7150/ijms.26571
    Bone loss in women commences before the onset of menopause and oestrogen deficiency. The increase of follicle-stimulating hormone (FSH) precedes oestrogen decline and may be a cause for bone loss before menopause. This review summarizes the current evidence on the relationship between FSH and bone derived from cellular, animal and human studies. Cellular studies found that FSH receptor (FSHR) was present on osteoclasts, osteoclast precursors and mesenchymal stem cells but not osteoblasts. FSH promoted osteoclast differentiation, activity and survival but exerted negligible effects on osteoblasts. Transgenic FSHR or FSH knockout rodents showed heterogenous skeletal phenotypes. Supplementation of FSH enhanced bone deterioration and blocking of FSH action protected bone of rodents. Human epidemiological studies revealed a negative relationship between FSH and bone health in perimenopausal women and elderly men but the association was attenuated in postmenopausal women. In conclusion, FSH may have a direct action on bone health independent of oestrogen by enhancing bone resorption. Its effects may be attenuated in the presence of overt sex hormone deficiency. More longitudinal studies pertaining to the effects of FSH on bone health, especially on fracture risk, should be conducted to validate this speculation.
    Matched MeSH terms: Osteoclasts*
  6. Ramli FF, Chin KY
    Diagnostics (Basel), 2020 Mar 06;10(3).
    PMID: 32155909 DOI: 10.3390/diagnostics10030145
    Bone turnover markers (BTMs) derived from the secretory activities of osteoblasts and the matrix-degrading activities of osteoclasts are useful in monitoring the progression of osteoporosis and the efficacy of anti-osteoporotic treatment. However, the usefulness of BTMs in predicting osteoporosis remains elusive. Osteocytes play a central role in regulating bone formation and resorption. The proteins secreted by osteocytes, such as fibroblast growth factor-23 (FGF23), sclerostin (SOST), and dickkopf-1 (DKK1), could be candidates for osteoporosis screening and fracture prediction. This review summarizes the current evidence on the potential of osteocyte-related proteins as biomarkers for osteoporosis and fracture prediction. The literature reports that SOST may be a potential marker for osteoporosis screening but not for fracture prediction. FGF23 is a potential marker for increased fracture risk, but more studies are needed to confirm its usefulness. The role of DKK1 as a marker to predict osteoporosis and fracture risk cannot be confirmed due to a lack of consistent evidence. In conclusion, circulating osteocyte markers are potential osteoporosis biomarkers, but more studies are warranted to validate their clinical use.
    Matched MeSH terms: Osteoclasts
  7. Radzi NFM, Ismail NAS, Alias E
    Curr Drug Targets, 2018;19(9):1095-1107.
    PMID: 29412105 DOI: 10.2174/1389450119666180207092539
    BACKGROUND: There are accumulating studies reporting that vitamin E in general exhibits bone protective effects. This systematic review, however discusses the effects of a group of vitamin E isomers, tocotrienols in preventing bone loss through osteoclast differentiation and activity suppression.

    OBJECTIVE: This review is aimed to discuss the literature reporting the effects of tocotrienols on osteoclasts, the cells specialized for resorbing bone.

    RESULTS: Out of the total 22 studies from the literature search, only 11 of them were identified as relevant, which comprised of eight animal studies, two in vitro studies and only one combination of both. The in vivo studies indicated that tocotrienols improve the bone health and reduce bone loss via inhibition of osteoclast formation and resorption activity, which could be through regulation of RANKL and OPG expression as seen from their levels in the sera. This is well supported by data from the in vitro studies demonstrating the suppression of osteoclast formation and resorption activity following treatment with tocotrienol isomers.

    CONCLUSION: Thus, tocotrienols are suggested to be potential antioxidants for prevention and treatment of bone-related diseases characterized by increased bone loss.

    Matched MeSH terms: Osteoclasts/drug effects; Osteoclasts/metabolism
  8. 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: Osteoclasts/drug effects; Osteoclasts/metabolism
  9. Morita H, Nugroho AE, Nagakura Y, Hirasawa Y, Yoshida H, Kaneda T, et al.
    Bioorg Med Chem Lett, 2014 Jun 1;24(11):2437-9.
    PMID: 24767841 DOI: 10.1016/j.bmcl.2014.04.020
    Four new chromone alkaloids, chrotacumines G-J (1-4), have been isolated from the barks of Dysoxylum acutangulum. Their structures and absolute configurations were elucidated on the basis of NMR and CD data. Chrotacumines G and J (1 and 4) showed osteoclast differentiation inhibitory activity in a dose dependent manner.
    Matched MeSH terms: Osteoclasts/cytology; Osteoclasts/drug effects*
  10. Hairi HA, Jusoh RR, Sadikan MZ, Hasan WNW, Shuid AN
    Int J Med Sci, 2025;22(4):819-833.
    PMID: 39991771 DOI: 10.7150/ijms.103241
    Moringa oleifera (MO) is renowned for its remarkable medicinal uses, supported by claims across various cultures and growing scientific evidence. Preclinical experimental evidence indicated that MO may effectively reduce bone loss and promote bone remodelling through its effects on osteoclasts and osteoblasts. In vivo studies demonstrated that MO enhances critical aspects of bone health, such as bone volume, trabecular thickness and overall bone density. Furthermore, MO positively influenced bone biomarkers including alkaline phosphatase and procollagen type 1 N-terminal propeptide, reflecting improved bone formation. Additionally, in vitro and ex vivo studies revealed that MO boosted bone regeneration, stimulated osteoblast activity and reduced inflammation. In terms of mechanisms, MO may modulate signalling pathways related to bone metabolism, such as BMP2, PI3K/Akt/FOXO1, p38α/MAPK14 and RANKL/RANK//OPG pathways. This evidence provides a strong foundation for future clinical research and potential therapeutic applications in managing and preventing bone loss conditions.
    Matched MeSH terms: Osteoclasts/drug effects; Osteoclasts/metabolism
  11. Erkus S, Turgut A, Kose O, Kalenderer O
    Malays Orthop J, 2019 Jul;13(2):42-44.
    PMID: 31467651 DOI: 10.5704/MOJ.1907.008
    Osteopetrosis (OP) is a rare hereditary sclerosing bone dysplasia characterised by generalised hard and brittle bone secondary to defective osteoclastic function. Osteopetrotic bone is brittle, thus these subjects are prone to frequent fractures, particularly of the long bones. Due to defective osteoclastic function, remodeling is also defective in OP. This report is a case of humeral fracture in a 9 years old girl who was followed seven years. The fracture had remodeled totally similar to healthy bone at the final follow-up. Conservative treatment should be kept in mind in the management of fractures in children with OP, and fractures within acceptable angulations and/or translations should be treated conservatively without hesitation.
    Matched MeSH terms: Osteoclasts
  12. Jayash SN, Hashim NM, Misran M, Baharuddin NA
    PeerJ, 2016;4:e2229.
    PMID: 27635307 DOI: 10.7717/peerj.2229
    The receptor activator of nuclear factor kappa-B (RANK)/RANK ligand/osteoprotegerin (OPG) system plays a critical role in bone remodelling by regulating osteoclast formation and activity. OPG has been used systemically in the treatment of bone diseases. In searching for more effective and safer treatment for bone diseases, we investigated newly formulated OPG-chitosan complexes, which is prepared as a local application for its osteogenic potential to remediate bone defects.
    Matched MeSH terms: Osteoclasts
  13. 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: Osteoclasts/drug effects; Osteoclasts/metabolism; Osteoclasts/pathology
  14. Neelakantan P, Ahmed HMA, Wong MCM, Matinlinna JP, Cheung GSP
    Int Endod J, 2018 Aug;51(8):847-861.
    PMID: 29377170 DOI: 10.1111/iej.12898
    The aim of this systematic review was to address the question: Do different irrigating protocols have an impact on the dislocation resistance of mineral trioxide aggregate (MTA)-based materials? The review was performed using a well-defined search strategy in three databases (PubMed, Scopus, Web of Science) to include laboratory studies performed between January 1995 and May 2017, in accordance with PRISMA guidelines. Two reviewers analysed the papers, assessed the risk of bias and extracted data on teeth used, sample size, size of root canal preparation, type of MTA-based material, irrigants, canal filling method, storage method and duration, region of roots and the parameters of push-out testing (slice thickness, plunger dimensions and plunger loading direction), the main results and dislocation resistance values (in MPa). From 255 studies, 27 were included for full-text analysis. Eight papers that met the inclusion criteria were included in this review. There was a wide variation in dislocation resistance due to differences in irrigation sequence, time and concentration of irrigants, storage method and duration, and the parameters of push-out bond strength testing. A meta-analysis was not done but qualitative synthesis of the included studies was performed. No definitive conclusion could be drawn to evaluate the effect of irrigation protocols on dislocation resistance of MTA-based materials. Recommendations have been provided for standardized testing methods and reporting of future studies, so as to obtain clinically relevant information and to understand the effects of irrigating protocols on root canal sealers and their interactions with the dentine walls of root canals.
    Matched MeSH terms: Osteoclasts/physiology
  15. Jolly JJ, Chin KY, Alias E, Chua KH, Soelaiman IN
    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: Osteoclasts/drug effects
  16. Mohamad NV, Soelaiman IN, Chin KY
    Clin Interv Aging, 2016;11:1317-1324.
    PMID: 27703340
    Osteoporosis is a condition causing significant morbidity and mortality in the elderly population worldwide. Age-related testosterone deficiency is the most important factor of bone loss in elderly men. Androgen can influence bone health by binding to androgen receptors directly or to estrogen receptors (ERs) indirectly via aromatization to estrogen. This review summarized the direct and indirect effects of androgens on bone derived from in vitro, in vivo, and human studies. Cellular studies showed that androgen stimulated the proliferation of preosteoblasts and differentiation of osteoblasts. The converted estrogen suppressed osteoclast formation and resorption activity by blocking the receptor activator of nuclear factor k-B ligand pathway. In animal studies, activation of androgen and ERα, but not ERβ, was shown to be important in acquisition and maintenance of bone mass. Human epidemiological studies demonstrated a significant relationship between estrogen and testosterone in bone mineral density and fracture risk, but the relative significance between the two remained debatable. Human experimental studies showed that estrogen was needed in suppressing bone resorption, but both androgen and estrogen were indispensable for bone formation. As a conclusion, maintaining optimal level of androgen is essential in preventing osteoporosis and its complications in elderly men.
    Matched MeSH terms: Osteoclasts/physiology
  17. 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: Osteoclasts/drug effects
  18. Moshiri A, Sharifi AM, Oryan A
    Clin Exp Pharmacol Physiol, 2016 Jul;43(7):659-84.
    PMID: 27061579 DOI: 10.1111/1440-1681.12577
    Simvastatin is a lipid lowering drug whose beneficial role on bone metabolism was discovered in 1999. Several in vivo studies evaluated its role on osteoporosis and fracture healing, however, controversial results are seen in the literature. For this reason, Simvastatin has not been the focus of any clinical trials as yet. This systematic review clears the mechanisms of action of Simvastatin on bone metabolism and focuses on in vivo investigations that have evaluated its role on osteoporosis and fracture repair to find out (i) whether Simvastatin is effective on treatment of osteoporosis and fracture repair, and (ii) which of the many available protocols may have the ability to be translated in the clinical setting. Simvastatin induces osteoinduction by increasing osteoblast activity and differentiation and inhibiting their apoptosis. It also reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts and their differentiation. Controversial results between the in vivo studies are mostly due to the differences in the route of administration, dose, dosage and carrier type. Local delivery of Simvastatin through controlled drug delivery systems with much lower doses and dosages than the systemic route seems to be the most valuable option in fracture healing. However, systemic delivery of Simvastatin with much higher doses and dosages than the clinical ones seems to be effective in managing osteoporosis. Simvastatin, in a particular range of doses and dosages, may be beneficial in managing osteoporosis and fracture injuries. This review showed that Simvastatin is effective in the treatment of osteoporosis and fracture healing.
    Matched MeSH terms: Osteoclasts/drug effects
  19. Mahendra DA, Yuliati A, Razali M, Kasim NHA, Firdauzy MAB, Roestamadji RI, et al.
    J Appl Oral Sci, 2025;33:e20240254.
    PMID: 39813520 DOI: 10.1590/1678-7757-2024-0254
    Guided bone regeneration (GBR) is an alternative treatment for craniofacial bone defects reconstruction through membrane barrier adaptation, such as demineralized dentin material membrane (DDMM). DDMM is used as a substitute for GBR material, which aligns with Green Economy principles, it has a good biological osteoinductive and osteoconductive effects, and its structure resembles bones. The balance of bone remodeling when experiencing craniofacial defects will be altered and allow changes to resorption activity, so the mechanisms of osteoclastogenesis and bone resorption are vital.

    OBJECTIVE: this article aims to analyze the expression of TNF-α, RANKL, and osteoclast cells count after application of DDMM as GBR in mandibular bone defects.

    METHODOLOGY: this is an experimental study with a post-test only control group design, which began with the randomization of 120 rats into five groups: K(-), without membrane implantation; K(+), PPCM; P1, DDMM; P2, DDMM + bone graft; P3, PPCM + bone graft. The expression of TNF-α, RANKL, and osteoclast cells count were observed, followed by analysis using a one-way ANOVA and post hoc Tukey HSD comparison test.

    RESULTS: there were significant differences in the expression of TNF-α, RANKL, and osteoclast cells count in all study groups (p=0.000). TNF-α showed a decreasing difference with the highest expression in the K(-) group on day 3 of 12.00±2.16. RANKL expression increased on day 14 and decreased on day 21 in all groups. The osteoclast cells count generally showed a critical period with the highest increase in the K(-) group on day 14 of 73.00±0.00.

    CONCLUSION: DDMM has the potential to be a superior membrane substitute compared to PPCM as GBR in alternative treatment for craniofacial bone defects reconstruction.

    Matched MeSH terms: Osteoclasts*
  20. 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: Osteoclasts/drug effects; Osteoclasts/physiology
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