Polyphenols and bone health -
Our goal was to supplement our subjects with additional elemental calcium mg in order to ensure that they receive total recommended calcium of mg mg. Similarly, the vitamin D supplementation we provided was to complement what the subjects were assumed to have received from diet and sun exposure, in order to reach the total daily recommendation.
Provision of placebo to the control and TC only groups increased the accuracy of the interventions, since it kept respondents blinded to the GTP treatment assignment. Participants in the placebo treatment group were provided mg of medicinal starch daily for 24 weeks.
Participants were instructed to take 1 capsule containing mg in the morning and another 1 capsule in the evening, after meals. Similar to those in the placebo treatment group, participants in the GTP treatment group were provided mg mg capsule × 2 per day of GTP per day for 24 weeks.
In addition to mg of medicinal startch daily, the TC training was held at the exercise hall of a local community center, for 60 minutes three times a week on three nonconsecutive days , for 24 weeks.
Each training session consisted of 10 minutes of warm-up exercise, 40 minutes of TC, and 10 minutes of cool-down exercise. The warm-up exercise featured movements of all major body joints that were involved in the subsequent TC exercise. Participants were taught by a qualified instructor the move simplified Yang-style TC [] for 40 minutes during each session.
The cool-down exercise involved whole body relaxation and deep breathing. Make-up sessions were offered to participants if necessary. A complete and accurate dietary assessment was needed to determine whether drastic dietary changes occurred during the intervention period that could affect outcome measures.
A 3-day dietary intake log was collected at the baseline, mid, and final visits and analyzed by Nutritionist Pro First Data Bank, Inc. A physical activity log was collected at the baseline, mid, and final visits to record any deviation from the usual activities.
All investigators, measurement and site personnel were blinded throughout this study. However, it was impossible to keep the TC instructor and the pharmacist, who distributed placebo or GTP capsules, blinded.
Fasting blood and urine samples morning after first empty of the bladder were collected for both primary and secondary outcome measures. Blood was drawn from a superficial arm vein with a syringe, transferred to a vacutainer, allowed to clot at room temperature, centrifuged at × g for 10 min within 2 hr of collection, and aliquoted from each collection.
During the visit for blood sample collection, urine samples were also collected in acid-washed polyethylene containers. Urine was aliquoted from each collection. All aliquoted blood and urine samples were stored in °C freezers prior to biochemical analyses.
Adherence to the intervention was evaluated by monitoring the consumption of capsules by pill count and attendance at TC training sessions. Compliance was determined as the percentage of all capsules ingested or possible group classes attended. Adverse effects associated with placebo or GTP treatment were self-reported by the participants if any, and by monitoring liver function monthly in the course of the intervention trial.
All observed or volunteered adverse events, regardless of suspected causal relationship to the study treatments, were recorded on the adverse event form throughout the study. Every participant was evaluated at baseline prior to starting intervention , 4, 12, and 24 weeks of intervention.
Biochemical markers of bone turnover have been shown to be promising in predicting fractures in the elderly up to 2 years before the event [ 53 ]. Assessing serum BAP a bone formation biomarker and serum TRAP a bone resorption biomarker could provide a more thorough clinical evaluation of bone status than BMD in predicting skeletal response to an exercise program and in monitoring bone resorption changes following initiation of exercise as early as month 3 [ 54 ].
The intra-assay CV of the BAP assay was 5. Such procedures are routinely performed in our laboratory [ 47 ]. The intra-assay variability was 2. In order to avoid the interassay variation, the samples from baseline, 4, 12, and 24 week visits of the same patients were measured for bone biomarkers withitn the same assay each time.
When ROS attack all macromolecules including lipids, proteins, and DNA, the addition of the hydroxyl group -OH to the C8-position of guanine produces C8-OH-adduct radical [ 55 ], which is subsequently converted to 8-OH-Guanine 8-OH-Gua by a one-electron oxidation [ 56 ].
While damaged lipids and proteins can be removed by metabolic turnover of molecules, impaired DNA has to be repaired in situ , or destroyed by apoptotic processes, if not to result in mutations. In humans, 8-OH-Glu glycosylase is the primary enzyme for the repair of 8-OH-Gua in a short-patch base-excision repair [ 57 ].
The excised form of 8-OH-Gua is 8-OHdG is excreted into urine without further metabolism and is stable for a significant time. Thus, urinary 8-OHdG generally reflects the whole body's oxidative DNA damage and repair, and becomes a putative biomarker for oxidative stress [ 58 ]. Detection of urinary 8-OHdG provides a sensitive and non-invasive means to evaluate the efficacy of dietary antioxidant supplements, such as GTP.
We measured urinary 8-OHdG levels in this study to evaluate the effect of treatments. The concentration of 8-OHdG, DNA damage oxidative stress biomarker, in urine was determined [ 48 ].
The urinary 8-OHdG was extracted from 1 ml urine with the Oasis ® HLB 3 cc 60 mg cartridge. The system consisted of double Solvent Delivery Modules Model pump , Autosampler Model with 4°C cool sample tray and column oven, CoulArray Electrochemical Detector Model A , and an Operating Computer.
The mobile phase consisted of buffer A 10 mM ammonium acetate, pH 4. Flow rate was kept at 0. The CoulArray Detector was set at , , , and mv; the highest peak appeared at mv channel. Authentic standard 8-OHdG was used for qualification by retention times and response patterns, and quantification by calibration curves.
The amount of 8-OHdG was adjusted by urinary creatinine level. Urinary creatinine level was determined colorimetrically with a Diagnostics Creatinine Kit Sigma Co.
The bioavailability of GTP was considered when we quantitatively evaluated the biological effects of GTP intervention. Therefore, we planed to measure the GTP levels in biofluid, such as serum and urine, of participants at baseline, 4, 12, and 24 weeks.
The procedures for analyzing serum and urinary GTP conjugates were modified from established protocols [ 48 , 59 ]. Briefly, serum μL or urine μL samples were incubated without enzyme, with betaglucuronidase units for serum and units for urine or with units of sulfatase at 37°C simultaneously for 1 h, to generate free GTP, free plus glucuronidated GTPs, free plus sulfated GTPs, and methylated GTPs, respectively.
The extracted samples were vacuum-dried and reconstituted for HPLC-CoulArray analysis. The HPLC-CoulArray system consists of double Solvent Delivery Modules Model pump , Autosampler Model with 4°C cool sample tray and column oven, CoulArray Electrochemical Detector Model A , and an Operating Computer.
The HPLC column was an Agilent Zorbax reverse-phase column, Eclipse XDB-C 18 5 μm, 4. Authentic standards were prepared with ascorbic acid. Calibration curves for individual GTP components were generated separately, and EGC, EC, EGCG and ECG were eluted at around 14, 21, 24 and 29 min, respectively.
The electrochemical detector was set at , , 70 and mV potentials, with the main peaks appearing at mV EGC , 70 mV EC, EGCG and mV ECG. Quality assurance and quality control procedures were taken during analyses, including analysis of authentic standards for every set of five samples and simultaneous analysis of spiked urine sample daily.
The limits of detection were 0. The levels of glucuronidated or sulfated GTP or methylated GTP were calculated by subtraction of free GTP levels from corresponding digestions. The four forms of GTP were pooled as a total for calculation of conjugation percentiles.
Due to the longitudinal design of the proposed study, a model of repeated measurements with random effect error terms was used. Statistical software SAS was employed to conduct the analyses, controlling for the within subject correlation. First, the measurements were compared across the 4 groups at the baseline.
In addition, participant characteristics were compared to detect whether participants in these four groups were different in certain characteristics. Second, the changes in the measurements from baseline to the follow-ups were calculated for each group.
We then tested whether these changes were statistically significant. Time-dependent trends, if any, were identified. For between-group differences, a two-way ANCOVA TC and GTP was conducted and controlled for within-subject correlation.
To control for the effect of age, body mass index, BMD, and other covariates i. Third, the characteristics of participants who dropped out were compared with those of the participants who stayed for the entire study period, in order to detect potential biases.
We have presented the rationale, design, and methodology of a placebo-controlled randomized trial, with quantitative studies, to investigate a new complementary and alternative medicine strategy featuring a dietary supplement and a mind-body exercise for alleviating bone loss in postmenopausal women with low bone mass.
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Food Chem Toxicol. Download references. This study was supported by R21AT from the National Center for Complementary and Alternative Medicine NCCAM of the National Institutes of Health. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM or the National Insititues of Heatlh.
We would like to thank Dr. Jay Magaziner Univeristy of Maryland, MD and Dr. Bahram H. Arjmandi Floride State University, FL for their advice. Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
Laura W Bush Institute for Women's Health, Texas Tech University Health Sciences Center, Lubbock, Texas, USA. Department of Laboratory Science and Primary Care, Texas Tech University Health Sciences Center, Lubbock, Texas, USA. Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
Department of Nutrition, Texas Tech University, Lubbock, Texas, USA. Department of Mechanical Engineering, Texas Tech University, Lubbock, Texas, USA. Department of Health, Exercise, and Sport Sciences, Texas Tech University, Lubbock, Texas, USA. Graduate Healthcare Engineering Option, Texas Tech University, Lubbock, Texas, USA.
In addition, via the NRF2 signaling pathway, GSTD promoted osteogenesis and maintained the balance between adipogenesis Treatment enhanced the expression of bone osteogenic markers, such as Bmp2 , Runx2 , Sp7 , and Bglap In addition, GSTD treatment enhanced the formation of calcium nodules, upregulating OB osteogenic differentiation and enhancing the maturation process of MC3T3-E1 cells Pre-treatment with GSTD for 1 h also significantly reduced DEX-induced apoptosis of OBs An in vitro study conducted by Zhou et al.
OCs were derived from BMM cells via RANKL and M-CSF stimulation. GSTD 2 and 10 µM suppressed RANKL-induced OC differentiation in the early stage of culture day 0—2 in a dose-dependent manner and attenuated OC differentiation at the terminal stage of culture by inhibiting the migration of OCs to resorb into the bone slice Moreover, GSTD reduced the expression of NFATc1 in BMM cells on days 1 — 3, which subsequently reduced the fusion and migration of pre-OCs by downregulating OC-specific gene expression, including the expression of TRAP, Ctsk, and Dcstamp Phenolic acid is another bioactive compound that exists in many plants.
In its structure, hydrogen atoms on benzene rings are replaced by a carboxylic acid group with at least one hydroxyl Benzoic acids gallic, p-hydroxybenzoic, vanillic, and syringic acid and cinnamic acid are the two major phenolic chemicals from which phenolic acid is generated caffeic, ferulic, sinapic, and p-coumaric acids Tannic acid TA is a naturally occurring polyphenol that is found in red wine, beer, coffee, black tea, green tea, grapes, pears, bananas, sorghum, black-eyed peas, lentils, and chocolate TA has been used as a food additive, a medication to treat diarrhea, a local astringent, an antidote for poisoning, and a remedy for burns It also possesses antioxidant, antimutagenic, and anticarcinogenic activities TA treatment is more effective in increasing hFOB 1.
Moreover, treatment of hFOB 1. Compared with cells treated with PAM, TA produced better results in terms of proliferation, morphological alterations, and mineralization In contrast, a study by Steffi et al. The treatment also reduced the OC number measured by total DNA on day 5 of culture Furthermore, the treatment reduced the actin ring formation of OCs The effects of phenolic acid on OBs and OCs are presented in Table 1.
Following consumption of coffee, vegetables, blueberries, and other fruits, a polyphenol molecule called 3 3-hydroxyphenyl propionic acid PPA , a phenolic acid that is generated by the gut microbiota, is released into the bloodstream 69 , The breakdown of chlorogenic acid by the gut microbiota results in the production of PPA, which is absorbed and oxidized in the liver before entering the circulation In addition, 24 h of treatment increased the mRNA expression of various OB differentiation markers, including Col1 and Spp1 Moreover, Zhao et al.
In addition, PPA treatment for 3 days inhibited RANKL-induced NFATc1, cFos, Mmp9, and Ctsk protein expression. PPA reduced the expression of the second messenger GPRA on the surface of pre-OCs, which increased the level of cAMP inside cells and inhibited the expression of OC-specific genes and OC development The BMP signal transduction pathway regulates OB formation and activation via both conventional Smad-dependent Bmp ligands, receptors, and Smads and non-canonical Smad-independent signaling pathways p38 MAPK pathway A previous study demonstrated that polyphenols promoted OB activation and development via the Smad-dependent signaling pathway 45 , Polyphenols upregulate Bmp2 and activate Smad proteins through a complex serine threonine receptor mechanism that subsequently induces the differentiation of bone marrow stem cells into OBs and modulates the expression of OB-related genes Runx2 , Alpl 45 , The roles of Runx2 include the establishment of the lineage of OBs from multipotent mesenchymal cells, promotion of early OB differentiation, and inhibition of late OB differentiation Runx2 regulates the expression of Sp7 , which is required for OB differentiation and bone formation, by directly binding to the Sp7 promoter 47 , Runx2 is also involved in the OB-selective expression of BSP when interaction occurs between two types of enhancers: a homeodomain protein-binding site the C site and two Runx2-binding sites, R1 and R2 Mmp13 is another example of an OB-specific gene that is influenced by Runx2 75 , Mmp13 is crucial in the bone remodeling process, and a study found that due to the manipulation of the OC lacunar-canalicular network remodeling in the cortical bone, Mmp13 -knockout mice had decreased resistance to fractures in their long bones, indicating that Mmp13 is required for the proper distribution of mineral density in cortical bone Furthermore, Runx2 downregulates the expression of Htra1 by binding to the Htra1 promoter at bp and bp, which subsequently promotes the osteoblastic differentiation of primary mesenchymal progenitor cells Runx2 determines the OB lineage from pluripotent mesenchymal cells, enhances OB differentiation at an early stage, and inhibits OB differentiation at a late stage.
Polyphenols increase the production of calcium, phosphorus, and Col1, which indicates OB mineralization and bone growth Some polyphenols, like 2S,3S -aromadendrinC-β-D-glucopyranoside AG from the extract of U. wallichiana , can protect the differentiated OBs from serum deprivation-induced apoptosis In addition, polyphenols stimulate OB formation and mineralization through the ER.
Estrogen-induced messengers are effectively transmitted in OBs by estrogen receptor alpha ERα Through ER signaling, polyphenols, like kaempferol, induce osteogenic differentiation of cultured OBs, which subsequently increases the transcription of numerous genes of bone differentiation markers Col1 , Runx2 , Bglap , Spp1 , and Sp7 OC precursors differentiate into mature OCs primarily through interactions with two cytokines: M-CSF and RANKL OC precursor cells require signals for proliferation and survival from M-CSF, which binds to colony-stimulating factor 1 receptor c-Fms , while RANKL-to-RANK interactions are important for differentiation, resorptive activity, and the survival of mature OCs When RANKL binds to RANK on pre-OCs, TRAF6 is recruited, which activates various transcription factors, such as MAPKs JNK, ERK, p38 , c-Fos, NF-κB, and NFATc1 39 , 50 , c-Fos is essential for the activation of activator protein-1 AP-1 , which interacts with NFATc1 This interaction regulates the expression of genes necessary for OC differentiation and subsequently regulates several OC-related genes, including TRAP , Mmp9 , Mmp13 , and Ctsk Polyphenols can reduce the RANKL-induced differentiation of OCs by inhibiting the expression of mRNAs related to OC differentiation, including TRAP, Ctsk , Mmp9 , Mmp13 , and NFATc1 in primary osteoclastic cells 33 , 51 , Tnfrsf11b, a soluble RANKL decoy receptor that is primarily generated by OBs, inhibits the interaction between RANKL and RANKL receptors, thereby hindering the development of OCs and inhibiting osteoclastic bone resorption Polyphenols inhibit the differentiation of bone marrow precursor cells to OCs in the presence of RANKL and M-CSF and suppress the activation of AKT 34 , Dcstamp is a multi-pass transmembrane protein, another master regulator of osteoclastogenesis that is essential for the cell—cell fusion of OC precursors during OC development 83 , Dcstamp possibly interacts with NFATc1 to ensure successful OC differentiation Zhou et al.
Figure 2 and Figure 3 summarize the targeted pathways involved in bone formation and the suppression of OC function and survival. According to Sieberath et al. This is due to the limitations and ethical issues faced when using animal models; therefore, if possible, they should be replaced with in vitro studies Co-culture provides a novel approach for the biological study of biomaterials, as the cellular environment in co-culture is closer to the in vivo environment than monoculture, with appropriate cell—cell interactions The co-culture model can be established both in 2D and 3D arrangement, with or without a direct physical contact among different cell types, and static or dynamic systems Figure 4 Co-culture methods involve the cultivation of two or more different cell types and can be performed in one culture dish or well either directly or indirectly In direct co-culture systems, cells are mixed in the culture environment and can make direct contact with each other Direct co-culture can be performed in almost any cell culture dish, for example, by layering two cell types on top of each other.
In contrast, indirect co-culture is performed by separating different cell types using inserted porous membranes Cells in direct co-culture can connect with each other in various ways, such as through gap junctions, tight junctions, and desmosomes Therefore, the direct co-culture system mimics in vivo conditions However, the inability to distinguish the different contributions of the diverse cell types, as the cells are mixed together in the same environment, is a clear disadvantage of direct co-culture Despite its simple set-ups, this methodology is associated with numerous technical difficulties, whereas indirect co-culture takes advantage of cell cultures inserted with porous membranes to keep the co-cultivated cell populations separate 24 , For example, in direct co-culture, the growth dominance of OBs causes the massive death of OCs, which is unfavorable for long-term culture Therefore, cell ratios must be optimized In addition, it is difficult to isolate a single type of cell from the co-culture system, which limits the methods available to analyze cells separately 24 , In indirect co-cultures, cells are physically separated; however, culture medium and other molecules, such as proteins, extracellular vesicles, and soluble factors, released by one cell type can still cross the pores and influence the behavior, proliferation, maturation, and differentiation of the other cell type s through paracrine signaling Moreover, cells can be evaluated separately, and cell migration can also be analyzed The limitation is that the physical receptor-mediated cell—cell interactions are hindered, and the large volumes of cells needed might limit the oxygen supply in the bottom wells 24 , In contrast, direct co-culture allows for a uniform medium height and oxygen supply for both cell types, and smaller volumes of cells are needed in direct co-culture than in transwell co-culture Osteoporosis is becoming a major public health problem, and its incidence is increasing.
Consequently, antiresorptive and anabolic therapies have been developed for the treatment of osteoporosis using various drugs and biomaterials with the purpose of stimulating bone formation or suppressing OC function and survival.
According to previous studies, polyphenols, especially bioactive phenolics, have positive effects on bone metabolism in osteoporosis. OBs and OCs are the most conventional cell types for studying bone diseases in vitro as these cells are the crucial components of osteogenesis and remodeling.
These cells do not behave independently of one another, and various communication pathways between them have been discovered. Therefore, it is imperative to further investigate the effects of polyphenols in co-culture models, as these models allow for optimal cell—cell interactions and mimic the in vivo environment more accurately than monoculture.
Hermizi Hapidin developed the idea for the study and coordinated the article; Nurul Husna Azizul collected most of the provided data and drafted the article; Hasmah Abdullah, Maryam Azlan, Azlina Ahmad, and Ima Nirwana Soleiman participated in the critical revision of the article; and all authors read and approved the final version of the article.
This work is licensed under a Creative Commons Attribution 4. Copyright Biomedpress. A partner of Crossref. Nurul Husna Azizul ×. Biomedicine Programme, School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia.
Hermizi Hapidin ×. Hasmah Abdullah ×. Maryam Azlan ×. Azlina Ahmad ×. Ima Nirwana Soelaiman ×. View Download Online Metrics ×. Statistics from Dimensions. ai Statistics from PlumX. Author Biography ×. Azizul, N. Potential Effects of Polyphenols on Osteoblast and Osteoclast Culture.
Biomedical Research and Therapy , 10 1 , Keywords: Osteoblast Osteoclast Polyphenol Bone remodeling. Polyphenols group and chemical structures of the different groups of polyphenols.
Download figure Enlarge figure. Table 1. Effects of polyphenols on OBs and OCs Polyphenols Bioactive compound Effects on OBs Effects on OCs Flavonoids 2S,3S -AromadendrinC-β-D-glucopyranoside AG from the extract of U.
wallichiana Himalayan Elm. Kaempferol [3,5,7-trihydroxy 4-hydroxyphenyl -4 H benzopyranone] Tsuchiya et al. Kim et al. Luteolin 3',4',5,7-tetrahydroxyflavone Melguizo-Rodríguez et al.
Stilbenes Piceatannol 3,3',4,5'-tetrahydroxy-trans-stilbene Chang et al. Yan et al. Lignan Gastrodin Liu et al. Phenolic acid Tannic acid Hapidin et al. Steffi et al. Zhao et al. Schematic representation of the potential effects of polyphenols on osteoblast OBs. Polyphenols upregulated bone morphogenetic protein-2 Bmp2 and activate Smad proteins through a complex serine threonine receptor mechanism which subsequently induce the differentiation of bone marrow stem cells into OBs and modulate the expression of OBs related genes such as the runt related transcription factor 2 Runx2 and alkaline phosphatase Alpl 45 , Runx2 is an important transcription factor of osteogenesis, as it regulates the expression of OBs differentiation marker genes including osterix Sp7 , osteopontin Spp1 , osteocalcin Bglap as well as collagen type 1 Col1 47 , Polyphenols also increased the production of calcium, phosphorus and Col1 which indicates OBs mineralization and bone growth Some polyphenols like 2S,3S -AromadendrinC-β-D-glucopyranoside AG from the extract of Ulmus wallichiana are able to protect the differentiated OBs from serum deprivation-induced apoptosis Kaempferol stimulates the osteogenic differentiation of cultured OBs by acting through the estrogen receptor ER signaling which subsequently increase the transcription of genes for several bone differentiation markers, Col1, Runx2, Bglap, Spp1 and Sp7 Schematic representation of potential effects of polyphenols on osteoclasts OCs.
Receptor activator of nuclear factor-κB ligand RANKL binds with RANK on preOCs, TNF receptor-associated factor TRAF 6 is recruited, which leads to activation of various transcription factors such as mitogen activated protein kinases MAPK including c-Jun N-terminal kinase JNK , extracellular signal-regulated kinase ERK , and p38, c-Fos, nuclear factor kappa B NF-κB , and nuclear factor of activated T-cell NFATc1 39 , c-Fos activate activator protein-1 AP-1 and interacts with NFATc1 33 , This regulates the expression of tartrate-resistant acid phosphatase TRAP , matrix metallopeptidase-9, 13 Mmp9, Mmp13 and cathepsin K Ctsk 3.
Polyphenols has been found to be able to reduce the RANKL-induced differentiation of OCs by inhibiting the expression of mRNAs related to OC differentiation, including TRAP, Ctsk, Mmp9, Mmp13 and NFATc1 in primary osteoclastic cells 33 , Osteoprotegerin Tnfrsf11b prevents OCs formation and osteoclastic bone resorption by inhibiting the RANKL—RANKL receptor interaction Polyphenols has been found to be able to inhibit OCs differentiation of bone marrow precursor cells to OCs in the presence of RANKL and M-CSF and suppressed the activation of AKT 34 , Dendritic cell-specific transmembrane protein Dcstamp possibly interact with NFATc1 for successful OCs differentiation Various technique of co-culture in in vitro model of bone remodeling process.
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Editor-in-Chief: Alessandro Aand Department of Pilyphenols and Healh Medicine Polyphwnols Polyphenols and bone health Primary Human Cells University of Pisa Pisa Italy. ISSN Print : ISSN Online Poolyphenols DOI: Background: Osteoporosis Vegan-friendly online stores B vitamin functions metabolic Polyphenols and bone health Blood sugar control myths debunked the bone mineral density and thus compromise the strength of the bones. Disease prevention through diet is the objective of the study and discussion. Among the several nutrients investigated, the intake of phenols seems to influence bone mineral density by acting as free radical scavengers, preventing oxidation-induced damage to bone cells. In addition, the growing understanding of the bone remodelling process supports the theory that inflammation significantly contributes to the etiopathogenesis of osteoporosis. B vitamin functions the B vitamin functions, a more Healh knowledge Polylhenols mechanisms hone B vitamin functions bone resorption processes has driven bbone to develop a compound library of many small Polyyphenols that specifically interfere with the genesis Polypheenols osteoclast nad cells. Natural compounds that suppress oxidative stress and Parkinsons disease commitment may have therapeutic value in treating pathologies associated with bone resorption like osteoporosis, rheumatoid arthritis, bone metastasis, and periodontal disease. The present review is focused on the current knowledge on the polyphenols derived from plants that could be efficacious in suppressing osteoclast differentiation and bone resorption. The strength and integrity of the human skeleton depends on a delicate balance between bone resorption and formation. Bone resorption represents a final step due to the interaction between cells that involve resorption of bone osteoclasts, OCand that synthetize bone matrix osteoblasts, OB.
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