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  1. 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*
  2. 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
  3. 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
  4. Fulltext Eurycoma longifolia: Medicinal Plant in the Prevention and Treatment of Male Osteoporosis due to Androgen Deficiency
    Mohd Effendy N, Mohamed N, Muhammad N, Naina Mohamad I, Shuid AN
    Evid Based Complement Alternat Med, 2012;2012:125761.
    PMID: 22844328 DOI: 10.1155/2012/125761
    Osteoporosis in elderly men is now becoming an alarming health issue due to its relation with a higher mortality rate compared to osteoporosis in women. Androgen deficiency (hypogonadism) is one of the major factors of male osteoporosis and it can be treated with testosterone replacement therapy (TRT). However, one medicinal plant, Eurycoma longifolia Jack (EL), can be used as an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with TRT. EL exerts proandrogenic effects that enhance testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodelling activity and reduce bone loss. Phytochemical components of EL may also prevent osteoporosis via its antioxidative property. Hence, EL has the potential as a complementary treatment for male osteoporosis.
    Matched MeSH terms: Osteoclasts
  5. Fulltext Curcumin Protects against Ovariectomy-Induced Bone Changes in Rat Model
    Hussan F, Ibraheem NG, Kamarudin TA, Shuid AN, Soelaiman IN, Othman F
    Evid Based Complement Alternat Med, 2012;2012:174916.
    PMID: 23049604 DOI: 10.1155/2012/174916
    Osteoporosis is a metabolic disease affecting both men and women especially in postmenopausal women. Curcumin possesses many medicinal properties. In this study, thirty two female Sprague-Dawley rats were used to determine the potential effect of curcumin in prevention of bone loss following ovariectomy. The animals were divided into Sham group, ovariectomised control, ovariectomised treated with curcumin 110 mg/kg and ovariectomised treated with Premarin 100 μg/kg. The treatments were given via daily oral gavages for 60 days. The structural parameters such as bone volume, trabecular number, trabecular thickness and trabecular separation were found to be deteriorated in ovariectomised rats compared to Sham group. Moreover, the reduced osteoblast count, the increased osteoclast count and increased eroded surface were found in ovariectomised groups. Treatment with curcumin was able to reverse all these ovariectomy-induced deteriorations. Curcumin treatment was as effective as Premarin in most parameters except the bone volume and eroded surface, which were better than Premarin. The high dose of curcumin treatment was not only able to reduce the osteoclast number but also increase the osteoblast count. Therefore, the potential effect of curcumin can be applied as an alternative to oestrogen for prevention of postmenopausal osteoporosis.
    Matched MeSH terms: Osteoclasts
  6. Fulltext An overview of bone cells and their regulating factors of differentiation
    Mohamed AM
    Malays J Med Sci, 2008 Jan;15(1):4-12.
    PMID: 22589609 MyJurnal
    Bone is a specialised connective tissue and together with cartilage forms the strong and rigid endoskeleton. These tissues serve three main functions: scaffold for muscle attachment for locomotion, protection for vital organs and soft tissues and reservoir of ions for the entire organism especially calcium and phosphate. One of the most unique and important properties of bone is its ability to constantly undergo remodelling even after growth and modelling of the skeleton have been completed. Remodelling processes enable the bone to respond and adapt to changing functional situations. Bone is composed of various types of cells and collagenous extracellular organic matrix, which is predominantly type I collagen (85-95%) called osteoid that becomes mineralised by the deposition of calcium hydroxyapatite. The non-collagenous constituents are composed of proteins and proteoglycans, which are specific to bone and the dental hard connective tissues. Maintenance of appropriate bone mass depends upon the precise balance of bone formation and bone resorption which is facilitated by the ability of osteoblastic cells to regulate the rate of both differentiation and activity of osteoclasts as well as to form new bone. An overview of genetics and molecular mechanisms that involved in the differentiation of osteoblast and osteoclast is discussed.
    Matched MeSH terms: Osteoclasts
  7. 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
  8. Fulltext A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health
    Chin KY, Pang KL, Mark-Lee WF
    Int J Med Sci, 2018;15(10):1043-1050.
    PMID: 30013446 DOI: 10.7150/ijms.25634
    Bisphenol A (BPA) is an endocrine disruptor which can bind to the oestrogen receptor. It also possesses oestrogenic, antiandrogenic, inflammatory and oxidative properties. Since bone responds to changes in sex hormones, inflammatory and oxidative status, BPA exposure could influence bone health in humans. This review aimed to summarize the current evidence on the relationship between BPA and bone health derived from cellular, animal and human studies. Exposure to BPA (0.5-12.5 µM) decreased the proliferation of osteoblast and osteoclast precursor cells and induce their apoptosis. Bisphenol AF (10 nM) enhanced transforming growth factor beta signalling but bisphenol S (10 nM) inhibited Wnt signalling involved in osteoblast differentiation in vitro. In animals, BPA and its derivatives demonstrated distinct effects in different models. In prenatal/postnatal exposure, BPA increased femoral bone mineral content in male rats (at 25 ug/kg/day) but decreased femoral mechanical strength in female mice (at 10 µg/kg/day). In oestrogen deficiency models, BPA improved bone mineral density and microstructures in aromatase knockout mice (at very high dose, 0.1% or 1.0% w/w diet) but decreased trabecular density in ovariectomized rats (at 37 or 370 ug/kg/day). In contrast, bisphenol A diglycidyl ether (30 mg/kg/day i.p.) improved bone health in normal male and female rodents and decreased trabecular separation in ovariectomized rodents. Two cross-sectional studies have been performed to examine the relationship between BPA level and bone mineral density in humans but they yielded negligible association. As a conclusion, BPA and its derivatives could influence bone health and a possible gender effect was observed in animal studies. However, its effects in humans await verification from more comprehensive longitudinal studies in the future.
    Matched MeSH terms: Osteoclasts/drug effects*
  9. 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
  10. An ex vivo culture model for orthodontically induced root resorption
    Wan Hassan WN, Stephenson PA, Waddington RJ, Sloan AJ
    J Dent, 2012 May;40(5):406-15.
    PMID: 22342686 DOI: 10.1016/j.jdent.2012.02.002
    Root resorption is a ubiquitous although undesirable sequela to orthodontic treatment. Current methods to investigate the pathophysiology have certain limitations. In pursuit to understand and develop treatment modalities for orthodontically induced root resorption, the ability to manipulate cells within their natural extracellular matrix in a three dimensional organotypic model is invaluable. The study aimed to develop a laboratory-based organotypic model to investigate the effect of orthodontic forces on the periodontium.
    Matched MeSH terms: Osteoclasts/classification; Osteoclasts/pathology
  11. Piper sarmentosum prevents glucocorticoid-induced osteoporotic bone resorption by increasing 11β-hydroxysteroid dehydrogenase type 1 activity
    Suhana MR, Farihah HS, Faizah O, Nazrun SA, Norazlina M, Norliza M, et al.
    Clin Ter, 2011;162(4):313-8.
    PMID: 21912818
    Osteoporosis is a proven complication of long-term glucocorticoid therapy. Concern on glucocorticoid induced osteoporosis has increased dramatically in recent years with the widespread use of synthetic glucocorticoids. Glucocorticoid action in bone depends upon the activity of 11βhydroxysteroid dehydrogenase type 1 enzyme (11βHSD1). This enzyme plays an important role in regulating corticosteroids by locally interconverting cortisone into active cortisol. This has been demonstrated in primary cultures of human, mouse or rat osteoblasts. Therefore, inhibition of this enzyme may reduce bone resorption markers. Piper sarmentosum (Ps) is a potent inhibitor of 11βHSD1 in liver and adipose tissue. In this study we determined the effect of Ps on 11βHSD1 activity in bones of glucocorticoid-induced osteoporotic rats.
    Matched MeSH terms: Osteoclasts/drug effects; Osteoclasts/enzymology
  12. Stable Incretin Mimetics Counter Rapid Deterioration of Bone Quality in Type 1 Diabetes Mellitus
    Mansur SA, Mieczkowska A, Bouvard B, Flatt PR, Chappard D, Irwin N, et al.
    J Cell Physiol, 2015 Dec;230(12):3009-18.
    PMID: 26016732 DOI: 10.1002/jcp.25033
    Type 1 diabetes mellitus is associated with a high risk for bone fractures. Although bone mass is reduced, bone quality is also dramatically altered in this disorder. However, recent evidences suggest a beneficial effect of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) pathways on bone quality. The aims of the present study were to conduct a comprehensive investigation of bone strength at the organ and tissue level; and to ascertain whether enzyme resistant GIP or GLP-1 mimetic could be beneficial in preventing bone fragility in type 1 diabetes mellitus. Streptozotocin-treated mice were used as a model of type 1 diabetes mellitus. Control and streptozotocin-diabetic animals were treated for 21 days with an enzymatic-resistant GIP peptide ([D-Ala(2) ]GIP) or with liraglutide (each at 25 nmol/kg bw, ip). Bone quality was assessed at the organ and tissue level by microCT, qXRI, 3-point bending, qBEI, nanoindentation, and Fourier-transform infrared microspectroscopy. [D-Ala2]GIP and liraglutide treatment did prevent loss of whole bone strength and cortical microstructure in the STZ-injected mice. However, tissue material properties were significantly improved in STZ-injected animals following treatment with [D-Ala2]GIP or liraglutide. Treatment of STZ-diabetic mice with [D-Ala(2) ]GIP or liraglutide was capable of significantly preventing deterioration of the quality of the bone matrix. Further studies are required to further elucidate the molecular mechanisms involved and to validate whether these findings can be translated to human patients.
    Matched MeSH terms: Osteoclasts/drug effects; Osteoclasts/metabolism
  13. Cathepsin K inhibitors: a novel target but promising approach in the treatment of osteoporosis
    Helali AM, Iti FM, Mohamed IN
    Curr Drug Targets, 2013 Dec;14(13):1591-600.
    PMID: 23957815
    Osteoporosis is a pathologic process characterized by low bone mass with skeletal fragility and an increased risk of fracture. It occurs due to an imbalance between bone resorption and formation. Although current antiresorptive therapy halts bone loss, it does not cure the condition as it also inhibits bone formation. Recent preclinical and clinical trials suggest that the inhibition of resorption by cathepsin K inhibitors increases bone formation. Cathepsin K is a papainlike cysteine protease with high potent collagenase activity and predominantly expressed in osteoclasts. While allowing demineralization, cathepsin K inhibitors suppress the degradation of type I collagen (the major organic matrix of bone) and thus enhancing bone formation. Many of these inhibitors have passed preclinical studies and are presently in clinical trials at different stages of advancement. This review explores the promising role of cathepsin K as a novel antiresorptive for the treatment of osteoporosis.
    Matched MeSH terms: Osteoclasts/metabolism
  14. 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
  15. Fulltext Eurycoma longifolia, a promising suppressor of RANKL-induced differentiation and activation of osteoclasts: An in vitro mechanistic evaluation
    Thu HE, Hussain Z, Mohamed IN, Shuid AN
    J Ayurveda Integr Med, 2018 08 16;10(2):102-110.
    PMID: 30120052 DOI: 10.1016/j.jaim.2017.07.014
    BACKGROUND: Eurycoma longifolia (E. longifolia) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Numerous in vivo studies have explored the effects of E. longifolia on osteoporosis; however, the in vitro cellular mechanism was not discovered yet.

    OBJECTIVES: The present study was aimed to investigate the effect of E. longifolia on the proliferation, differentiation and maturation of osteoclasts and the translational mechanism of inhibition of osteoclastogenesis using RAW 264.7 cells as an in vitro osteoclastic model.

    MATERIALS AND METHODS: Having assessed cytotoxicity, the cell viability, cell proliferation rate and osteoclastic differentiation capacity of E. longifolia was investigated by evaluating the tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclasts. Taken together, the time-mannered expression of osteoclast-related protein biomarkers such as matrix metallopeptidase-9 (MMP-9), cathepsin-K, TRAP, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), superoxide (free radicals) generation and superoxide dismutase activity were also measured to comprehend the mechanism of osteoclastogenesis.

    RESULTS: E. longifolia did not show significant effects on cytotoxicity and cell proliferation of RAW 264.7 cells; however, a significant inhibition of cells differentiation and maturation of osteoclasts was observed. Moreover, a significant down-regulation of RANKL-induced TRAP activity and expression of MMP-9, cathepsin-K, TRAP, NFATc1 and generation of superoxide and enhanced superoxide dismutase activity was observed in E. longifolia treated cell cultures.

    CONCLUSION: We anticipated that E. longifolia that enhances bone regeneration on the one hand and suppresses osteoclast's maturation on the other hand may have great therapeutic value in treating osteoporosis and other bone-erosive diseases such as rheumatoid arthritis and metastasis associated with bone loss.

    Matched MeSH terms: Osteoclasts
  16. Fulltext Two different isomers of vitamin e prevent bone loss in postmenopausal osteoporosis rat model
    Muhammad N, Luke DA, Shuid AN, Mohamed N, Soelaiman IN
    Evid Based Complement Alternat Med, 2012;2012:161527.
    PMID: 23118785 DOI: 10.1155/2012/161527
    Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function, a condition associated with increased free radicals. Vitamin E, a lipid-soluble vitamin, is a potent antioxidant which can scavenge free radicals in the body. In this study, we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats. Three-month-old female Wistar rats were randomly divided into ovariectomized control, sham-operated, and ovariectomized rats treated with either alpha-tocopherol or tocotrienol. Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis. Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume (BV/TV) and trabecular number (Tb.N) and an increase in trabecular separation (Tb.S). The increase in osteoclast surface (Oc.S) and osteoblast surface (Ob.S) in ovariectomy indicates an increase in bone turnover rate. Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb.N as well as the increase in Tb.S, while reducing the Oc.S and increasing the Ob.S. In conclusion, the two forms of vitamin E were able to prevent bone loss due to ovariectomy. Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model.
    Matched MeSH terms: Osteoclasts
  17. Fulltext The effects of tualang honey on bone metabolism of postmenopausal women
    Mohd Effendy N, Mohamed N, Muhammad N, Mohamad IN, Shuid AN
    Evid Based Complement Alternat Med, 2012;2012:938574.
    PMID: 22973408 DOI: 10.1155/2012/938574
    Osteoporosis which is characterized by low bone mass and microarchitectural deterioration with a consequent increase in bone fragility can be associated with various stimuli such as oxidative stress and inflammation. Postmenopausal women are more prone to osteoporosis due to reduction in estrogen which may further lead to elevation of oxidative stress and lipid accumulation which will promote osteoblasts apoptosis. Proinflammatory cytokines are elevated following estrogen deficiency. These cytokines are important determinants of osteoclasts differentiation and its bone resorption activity. The main treatment for postmenopausal osteoporosis is estrogen replacement therapy (ERT). Despite its effectiveness, ERT, however, can cause many adverse effects. Therefore, alternative treatment that is rich in antioxidant and can exert an anti-inflammatory effect can be given to replace the conventional ERT. Tualang honey is one of the best options available as it contains antioxidant as well as exerting anti-inflammatory effect which can act as a free radical scavenger, reducing the oxidative stress level as well as inhibiting proinflammatory cytokine. This will result in survival of osteoblasts, reduced osteoclastogenic activity, and consequently, reduce bone loss. Hence, Tualang honey can be used as an alternative treatment of postmenopausal osteoporosis with minimal side effects.
    Matched MeSH terms: Osteoclasts
  18. Noni leaf and black tea enhance bone regeneration in estrogen-deficient rats
    Shalan NA, Mustapha NM, Mohamed S
    Nutrition, 2017 Jan;33:42-51.
    PMID: 27908549 DOI: 10.1016/j.nut.2016.08.006
    OBJECTIVE: Black tea and Nonileaf are among the dietary compounds that can benefit patients with bone resorption disorders. Their bone regeneration effects and their mechanisms were studied in estrogen-deficient rats.

    METHODS: Noni leaves (three doses) and black tea water extracts were fed to ovariectomized rats for 4 mo, and their effects (analyzed via mechanical measurements, micro-computed tomography scan, and reverse transcriptase polymerase chain reaction mRNA) were compared with Remifemin (a commercial phytoestrogen product from black cohosh).

    RESULTS: The water extracts (dose-dependently for noni leaves) increased bone regeneration biomarker (runt-related transcription factor 2, bone morphogenetic protein 2, osteoprotegerin, estrogen receptor 1 [ESR1], collagen type I alpha 1A) expressions and reduced the inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, nuclear factor [NF]-κB, and receptor activator of NF-κB ligand) mRNA expressions/levels in the rats. The extracts also improved bone physical and mechanical properties. The extracts demonstrated bone regeneration through improving bone size and structure, bone mechanical properties (strength and flexibility), and bone mineralization and density.

    CONCLUSIONS: The catechin-rich extract favored bone regeneration and suppressed bone resorption. The mechanisms involved enhancing osteoblast generation and survival, inhibiting osteoclast growth and activities, suppressing inflammation, improving bone collagen synthesis and upregulating ESR1 expression to augment phytoestrogenic effects. Estrogen deficiency bone loss and all extracts studied (best effect from Morinda leaf at 300 mg/kg body weight) mitigated the loss, indicating benefits for the aged and menopausal women.

    Matched MeSH terms: Osteoclasts/drug effects
  19. Bisphenol A exposure disturbs the bone metabolism: An evolving interest towards an old culprit
    Thent ZC, Froemming GRA, Muid S
    Life Sci, 2018 Apr 01;198:1-7.
    PMID: 29432759 DOI: 10.1016/j.lfs.2018.02.013
    Bisphenol A (BPA) (2,2,-bis (hydroxyphenyl) propane), a well-known endocrine disruptor (ED), is the exogenous chemical that mimic the natural endogenous hormone like oestrogen. Due to its extensive exposure to humans, BPA is considered to be a major toxicological agent for general population. Environmental exposure of BPA results in adverse health outcomes including bone loss. BPA disturbs the bone health by decreasing the plasma calcium level and inhibiting the calcitonin secretion. BPA also stimulated differentiation and induced apoptosis in human osteoblasts and osteoclasts. However, little is known about the underlying mechanisms of the untoward effect of BPA against bone metabolism. The present review gives an overview on the possible mechanisms of BPA towards bone loss. The previous literature shows that BPA exerts its toxic effect on bone cells by binding to the oestrogen related receptor-gamma (ERγ), reducing the bone morphogenic protein-2 (BMP-2) and alkaline phosphatase (ALP) activities. BPA interrupts the bone metabolism via RANKL, apoptosis and Wnt/β-catenin signaling pathways. It is, however, still debated on the exact underlying mechanism of BPA against bone health. We summarised the molecular evidences with possible mechanisms of BPA, an old environmental culprit, in bone loss and enlightened the underlying understanding of adverse action of BPA in the society.
    Matched MeSH terms: Osteoclasts/drug effects
  20. Fulltext The immunologic properties of undifferentiated stem cells from human exfoliated deciduous teeth (SHED) and its potential application in bone regeneration
    Nurul, A.A., Tan, S.J., Asiah, A.B., Norliana, G., Nor Shamsuria, O., Nurul, A.S.
    International Medical Journal Malaysia, 2013;12(1):19-26.
    MyJurnal
    Introduction: Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative, clonogenic cells capable of differentiating into osteoblasts and inducing bone formation. It is a potential alternative for stem cell bone regeneration therapy. However, stem cell therapy carries the risk of immune rejection mediated by inflammatory cytokines of the human defense system. Objective: This preliminary research studies the interaction between SHED and the immune system by determining the inflammatory cytokines profile and osteogenic potential of SHED. Methods: Human fetal osteoblasts (hFOb) cell line and isolated SHED were cultured and total RNA was extracted, followed by reverse transcription cDNA synthesis. Semi-quantitative reverse transcription PCR and Multiplex PCR were performed to detect the expression levels of OPG/RANKL and TNF-α, IL-1β, IL-6, IL-8 and TGF-β in both cell types. Results: Analysis showed that SHED expressed significantly lower amounts of IL-1β, IL-6, and IL-8 compared to hFOB. IL-1β is a potent bone-resorbing factor, while IL-6 and IL-8 induce osteoclastogenesis and osteolysis respectively. SHED did not express TNF-α which stimulates osteoclastic activity. SHED demonstrated high OPG/RANKL ratio, in contrast with that of marrow stem cells described in previous studies. Our findings suggest that SHED may have improved immunomodulatory profile in terms of promoting relatively lower inflammatory reaction during transplant and enhancing bone regeneration. Conclusion: SHED has a potential to be a good source of osteoblasts for bone regeneration therapy. Further studies on the immunomodulatory properties of SHED-derived osteoblasts are necessary to enable stem cell therapy in immunocompetent hosts.
    Matched MeSH terms: Osteoclasts
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