title: Estrogen inhibits RANKL-induced osteoclastic differentiation by increasing the expression of TRPV5 channel.
abstract: The inhibitor effect of estrogen on osteoclasts differentiation is very important in the etiology of estrogen protecting the adult skeleton against bone loss. However, the precise molecular events underlying the effect of estrogen on osteoclasts differentiation are not known. Recent studies implicated an important role of transient receptor potential vanilloid 5 (TRPV5) in osteoclast differentiation and bone resorption. Furthermore, some studies have confirmed that estrogen is involved in the regulation of calcium ion (Ca(2+)) influx in many cells via TRPV5 channel. Therefore, we hypothesize that TRPV5 channel may be implicated in the process of estrogen-inhibited osteoclastogenesis and bone resorption. Western blot, quantitative real-time PCR, tartrate-resistant acid phosphatase (TRAP) staining, and pit formation assay were employed to investigate the role of TRPV5 in estrogen decreasing osteoclast differentiation and bone resorption. We found that the expression of TRPV5 is significantly down-regulated during estrogen deficiency-induced osteoclastogenesis. Furthermore, TRAP staining and pit formation assay showed that the depletion of TRPV5 significantly blocks the inhibitor effects of estrogen on osteoclasts differentiation and bone resorption activity. Further studies confirmed that estrogen regulates the expression of TRPV5 channel via estrogen receptor. Based on these results above, we can draw conclusion that TRPV5 may contribute to the process of estrogen-inhibited osteoclastogenesis and bone resorption activity.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Fangjing
authors.initials: F
authors.lastname: Chen
authors.forename: Yueping
authors.initials: Y
authors.lastname: Ouyang
authors.forename: Tianwen
authors.initials: T
authors.lastname: Ye
authors.forename: Bin
authors.initials: B
authors.lastname: Ni
authors.forename: Aimin
authors.initials: A
authors.lastname: Chen
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000235:genetics; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000097:blood / Q000378:metabolism*; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010052:Ovariectomy; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D015220:Calcium Channels; D004967:Estrogens; D007527:Isoenzymes; D053245:RANK Ligand; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C485717:Trpv2 protein, mouse; C486576:Trpv4 protein, mouse; C492240:Trpv5 protein, mouse; C446923:Trpv6 protein, mouse; D004958:Estradiol; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: ESTROGEN; OSTEOCLASTOGENESIS; OSTEOPOROSIS; TRPV5