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Fulltext Tocotrienols Regulate Bone Loss through Suppression on Osteoclast Differentiation and Activity: A Systematic Review

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
In vitro evaluation of osteoprotegerin in chitosan for potential bone defect applications

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
Fulltext Local application of osteoprotegerin-chitosan gel in critical-sized defects in a rabbit model

Jayash SN, Hashim NM, Misran M, Baharuddin NA

PeerJ, 2017;5:e3513.
PMID: 28674665 DOI: 10.7717/peerj.3513

BACKGROUND: Osteoprotegerin (OPG) is used for the systemic treatment of bone diseases, although it has many side effects. The aim of this study was to investigate a newly formulated OPG-chitosan gel for local application to repair bone defects. Recent studies have reported that immunodetection of osteopontin (OPN) and osteocalcin (OC) can be used to characterise osteogenesis and new bone formation.
METHODS: The osteogenic potential of the OPG-chitosan gel was evaluated in rabbits. Critical-sized defects were created in the calvarial bone, which were either left unfilled (control; group I), or filled with chitosan gel (group II) or OPG-chitosan gel (group III), with rabbits sacrificed at 6 and 12 weeks. Bone samples from the surgical area were decalcified and treated with routine histological and immunohistochemical protocols using OC, OPN, and cathepsin K (osteoclast marker) antibodies. The toxicity of the OPG-chitosan gel was evaluated by biochemical assays (liver and kidney function tests).
RESULTS: The mean bone growth in defects filled with the OPG-chitosan gel was significantly higher than those filled with the chitosan gel or the unfilled group (p

Matched MeSH terms: Osteoclasts
Effect of root canal irrigation protocols on the dislocation resistance of mineral trioxide aggregate-based materials: A systematic review of laboratory studies

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
Fulltext Can telomere length predict bone health? A review of current evidence

Wong SK, Ima-Nirwana S, Chin KY

Bosn J Basic Med Sci, 2020 Nov 02;20(4):423-429.
PMID: 32156247 DOI: 10.17305/bjbms.2020.4664

Telomeres are repetitive DNA sequences located at the end of chromosomes that serve as a protective barrier against chromosomal deterioration during cell division. Approximately 50-200 base pairs of nucleotides are lost per cell division, and new repetitive nucleotides are added by the enzyme telomerase, allowing telomere maintenance. Telomere shortening has been proposed as an indicator for biological aging, but its relationship with age-related osteoporosis is ambiguous. We summarize the current evidence on the relationship between telomere length and bone health in experimental and epidemiological studies, which serve as a scientific reference for the development of novel diagnostic markers of osteoporosis or novel therapeutics targeting telomere and telomerase of bone cells to treat osteoporosis.

Matched MeSH terms: Osteoclasts/metabolism
A concise review of testosterone and bone health

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
Fulltext The Relationship between Follicle-stimulating Hormone and Bone Health: Alternative Explanation for Bone Loss beyond Oestrogen?

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*
Fulltext A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures

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
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: Osteoclasts/drug effects
Regulation of ITAM adaptor molecules and their receptors by inhibition of calcineurin-NFAT signalling during late stage osteoclast differentiation

Zawawi MS, Dharmapatni AA, Cantley MD, McHugh KP, Haynes DR, Crotti TN

Biochem Biophys Res Commun, 2012 Oct 19;427(2):404-9.
PMID: 23000414 DOI: 10.1016/j.bbrc.2012.09.077

Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcRγ) and DNAX-activating protein 12kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin (β3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that FK506 treatment significantly (p<0.05) reduced the expression of NFATc1, CathK, OSCAR, FcRγ, TREM2 and DAP12 during the terminal stage of osteoclast formation. VIVIT treatment significantly (p<0.05) decreased CathK, OSCAR, FcRγ, and AnnVIII, gene expression. This data suggest FK506 and VIVIT act differently in targeting the calcineurin-NFAT signalling cascade to suppress key mediators of the ITAM pathway during late stage osteoclast differentiation and this is associated with a reduction in both osteoclast differentiation and activity.

Matched MeSH terms: Osteoclasts/cytology*; Osteoclasts/metabolism
Fulltext The Influence of Ficus deltoidea in Preserving Alveolar Bone in Ovariectomized Rats

Omar NI, Baharin B, Lau SF, Ibrahim N, Mohd N, Ahmad Fauzi A, et al.

Vet Med Int, 2020;2020:8862489.
PMID: 33456747 DOI: 10.1155/2020/8862489

Ficus deltoidea has been shown to possess antioxidant properties that could prevent the development of chronic inflammatory bone diseases. In this study, the efficacy of F. deltoidea in preventing alveolar bone resorption in osteoporotic rats induced by ovariectomy (OVX) was investigated. Twenty-four female Wistar rats were divided into four groups (n = 6) consisting of sham-operated (SO), ovariectomized control (OVXN), ovariectomized treated with estrogen (OVXP), and ovariectomized treated with F. deltoidea extract (OVXF). At the beginning of the study, two nonovariectomized, healthy rats were sacrificed to serve as baseline (BL). Treatment of the rats commenced two weeks after ovariectomy-the OVXP rats that served as positive control received Premarin® (64.5 μg/kg body weight), while OVXF rats were given F. deltoidea (800 mg/kg body weight); both agents were administered orally for two months. The negative control group of rats (OVXN) and the SO group received deionized water, also administered via oral gavage. At necropsy, morphometric assessment of the interradicular bone of the first molar was carried out using a micro-CT scanner, while quantification of osteoclasts and osteoblasts was performed histologically. The results showed that no statistically significant differences among the groups (p > 0.05) for bone morphometric assessment. However, trabecular thickness in the OVXF group was similar to BL, while trabecular separation and alveolar bone loss height were lower than those of the OVXN group. Histologically, the OVXF group demonstrated a significantly lower number of osteoclasts and a higher number of osteoblasts compared with OVXN (p=0.008 and p=0.019, respectively; p < 0.05). In conclusion, F. deltoidea has the capacity to prevent alveolar bone loss in ovariectomy-induced osteoporosis rats by potentially preserving trabecular bone microarchitecture and to decrease osteoclast and increase osteoblast cell count.

Matched MeSH terms: Osteoclasts
Regulatory actions of 3',5'-cyclic adenosine monophosphate on osteoclast function: possible roles of Epac-mediated signaling

Jeevaratnam K, Salvage SC, Li M, Huang CL

Ann N Y Acad Sci, 2018 Dec;1433(1):18-28.
PMID: 29846007 DOI: 10.1111/nyas.13861

Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP]i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated Gs -protein activation known to increase [cAMP]i , unaccompanied by the [Ca2+ ]i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed.

Matched MeSH terms: Osteoclasts/cytology; Osteoclasts/drug effects; Osteoclasts/metabolism*
Fulltext The Effects of Annatto Tocotrienol Supplementation on Cartilage and Subchondral Bone in an Animal Model of Osteoarthritis Induced by Monosodium Iodoacetate

Chin KY, Wong SK, Japar Sidik FZ, Abdul Hamid J, Abas NH, Mohd Ramli ES, et al.

Int J Environ Res Public Health, 2019 08 13;16(16).
PMID: 31412648 DOI: 10.3390/ijerph16162897

Osteoarthritis is a degenerative joint disease which primarily affects the articular cartilage and subchondral bones. Since there is an underlying localized inflammatory component in the pathogenesis of osteoarthritis, compounds like tocotrienol with anti-inflammatory properties may be able to retard its progression. This study aimed to determine the effects of oral tocotrienol supplementation on the articular cartilage and subchondral bone in a rat model of osteoarthritis induced by monosodium iodoacetate (MIA). Thirty male Sprague-Dawley rats (three-month-old) were randomized into five groups. Four groups were induced with osteoarthritis (single injection of MIA at week 0) and another served as the sham group. Three of the four groups with osteoarthritis were supplemented with annatto tocotrienol at 50, 100 and 150 mg/kg/day orally for five weeks. At week 5, all rats were sacrificed, and their tibial-femoral joints were harvested for analysis. The results indicated that the groups which received annatto tocotrienol at 100 and 150 mg/kg/day had lower histological scores and cartilage remodeling markers. Annatto tocotrienol at 150 mg/kg/day significantly lowered the osteocalcin levels and osteoclast surface of subchondral bone. In conclusion, annatto tocotrienol may potentially retard the progression of osteoarthritis. Future studies to confirm its mechanism of joint protection should be performed.

Matched MeSH terms: Osteoclasts
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: Osteoclasts/drug effects; Osteoclasts/metabolism; Osteoclasts/pathology
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: Osteoclasts/cytology; Osteoclasts/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: Osteoclasts/drug effects; Osteoclasts/metabolism
Optimization of the Static Human Osteoblast/Osteoclast Co-culture System

Jolly JJ, Chin KY, Farhana MFN, Alias E, Chua KH, Hasan WNW, et al.

Iran J Med Sci, 2018 Mar;43(2):208-213.
PMID: 29749990

Osteoblasts (OBs) and osteoclasts (OCs) are 2 major groups of bone cells. Their cell-to-cell interactions are important to ensure the continuity of the bone-remodeling process. Therefore, the present study was carried out to optimize an OB/OC co-culture system utilizing the human OB cell line hFOB 1.19 and OCs extracted from peripheral blood mononuclear cells (PBMNCs). It was a 2-step procedure, involving the optimization of the OB culture and the co-culture of the OBs with PBMNCs at an optimum ratio. Firstly, pre-OBs were cultured to 90% confluency and the time required for differentiation was determined. OB differentiation was determined using the van Gieson staining to detect the presence of collagen and Alizarin Red for calcium. Secondly, OBs and OCs were co-cultured at the ratios of 1 OC: 1 OB, 1 OC: 4 OBs, 2 OCs: 1 OB, and 1 OC: 2 OBs. Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the differentiation of the OCs. The results showed that collagen was present on day 1, whereas calcium was detected as early as day 3. Based on the result of TRAP staining, 1 OC: 2 OBs was taken as the most appropriate ratio. No macrophage colony-stimulating factor and receptor activator of the nuclear factor-κB ligand were added because they were provided by the OBs. In conclusion, these optimization processes are vital as they ensure the exact time point and ratio of the OB/OC co-culture in order to produce a reliable and reproducible co-culture system.

Matched MeSH terms: Osteoclasts
Fulltext Vitamin E as an Antiosteoporotic Agent via Receptor Activator of Nuclear Factor Kappa-B Ligand Signaling Disruption: Current Evidence and Other Potential Research Areas

Chin KY, Ima-Nirwana S

Evid Based Complement Alternat Med, 2012;2012:747020.
PMID: 22919420 DOI: 10.1155/2012/747020

Osteoporosis is a growing healthcare burden that affects the quality of life in the aging population. Vitamin E is a potential prophylactic agent that can impede the progression of osteoporosis. Various in vivo studies demonstrated the antiosteoporotic potential of vitamin E, but evidence on its molecular mechanism of action is limited. A few in vitro studies showed that various forms of vitamin E can affect the receptor activator of nuclear factor kappa-B ligand (RANKL) signaling and their molecular targets, thus preventing the formation of osteoclasts in the early stage of osteoclastogenesis. Various studies have also shown that the effects of the different isoforms of vitamin E differ. The effects of single isoforms and combinations of isoforms on bone metabolism are also different. Vitamin E may affect bone metabolism by disruption of free radical-mediated RANKL signaling, by its oestrogen-like effects, by its effects on the molecular mechanism of bone formation, by the anti-inflammatory effects of its long-chain metabolites on bone cells, and by the inhibition of 3-hydroxyl-3-methyglutaryl coenzyme A (HMG-CoA). In conclusion, the vitamin E isoforms have enormous potential to be used as prophylactic and therapeutic agents in preventing osteoporosis, but further studies should be conducted to elucidate their mechanisms of action.

Matched MeSH terms: Osteoclasts
Chrotacumines G-J, chromone alkaloids from Dysoxylum acutangulum with osteoclast differentiation inhibitory activity

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*
Remodelling of Humeral Fracture in a Child with Osteopetrosis Tarda following Conservative Management - A 7-year Follow-up: A Case Report

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

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