{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:54:44Z","timestamp":1787655284637,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800781"],"award-info":[{"award-number":["81800781"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the changes in proinflammatory cytokines and chemokines, namely, C\u2010C motif ligand (CCL) 2 and CCL7, in postmenopausal osteoporosis (PMOP) and to develop a new drug, bindarit (Bnd), for PMOP in an ovariectomized (OVX) mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bone marrow macrophages (BMMs) from the femurs of five women with PMOP and five premenopausal women without osteoporosis were detected by RNA sequencing. BMMs from mice were differentiated into osteoclasts and treated with a synthetic inhibitor of CCL2 and CCL7, Bnd, or 17 beta estradiol (E<jats:sub>2<\/jats:sub>). Mouse BMMs were differentiated into osteoclasts with or without Bnd for 7\u2009days and analyzed by RNA sequencing. Osteoblasts of mice were induced to undergo osteoblastogenesis and treated with Bnd. OVX mice were treated with E<jats:sub>2<\/jats:sub> or Bnd after surgery. The protein and mRNA expression of CCL2 and CCL7 was detected using immunostaining and qPCR, respectively, in OVX and aged mice and in cells cultured <jats:italic>in vitro<\/jats:italic>. Osteoclast formation was detected using a tartrate\u2010resistant acid phosphatase (TRAP) assay <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Alkaline phosphatase (ALP), runt\u2010related transcription factor 2 (Runx2) and osteocalcin (OCN) were detected using immunostaining to evaluate osteogenesis. Microcomputed tomography was conducted to analyze trabecular bone parameters, the structure model index, bone mineral density and other variables. Nuclear factor\u2010\u03baB (NF\u2010\u03baB) signaling pathway\u2010related protein phosphorylation of IKK\u03b1\/\u03b2 (p\u2010IKK\u03b1\/\u03b2) and p\u2010NF\u03baB p65 was examined using western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CCL2, CCL7 and their receptor of C\u2010C chemokine receptor\u20102 (CCR2), and the NF\u2010\u03baB signaling pathway, were significantly increased in women with PMOP. CCL2 and CCL7 protein and mRNA expression was increased in OVX mice and aged female mice, but the increases were attenuated by E<jats:sub>2<\/jats:sub> and Bnd. E<jats:sub>2<\/jats:sub> and Bnd effectively inhibited osteoclastogenesis and the protein expression of CCL2 and CCL7 both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> and reduced bone loss in OVX mice. Bnd did not affect the mineralization of osteoblasts directly <jats:italic>in vitro<\/jats:italic> but reduced bone turnover <jats:italic>in vivo<\/jats:italic>. p\u2010IKK\u03b1\/\u03b2 and p\u2010NF\u03baB p65 levels were increased in BMMs of mice after differentiation into osteoclasts but were significantly decreased by Bnd.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The proinflammatory cytokines and chemokines CCL2, CCL7 and CCR2 were correlated with PMOP. Bnd attenuated the increases in CCL2 and CCL7 levels to affect osteoporosis in OVX mice <jats:italic>via<\/jats:italic> the NF\u03baB signaling pathway. Thus, Bnd may be useful as a new therapeutic for the prevention of PMOP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.13252","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T07:59:19Z","timestamp":1650959959000},"page":"1203-1216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Bindarit Reduces Bone Loss in Ovariectomized Mice by Inhibiting <scp>CCL2<\/scp> and <scp>CCL7<\/scp> Expression <i>via<\/i> the <scp>NF\u2010\u03baB<\/scp> Signaling Pathway"],"prefix":"10.1111","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3781-6786","authenticated-orcid":false,"given":"Shi\u2010guo","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Hainan Province Hospital of Traditional Chinese Medicine  Haikou Hainan China"},{"name":"Center for Orthopaedic Surgery, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases The Third Affiliated Hospital of Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010ling","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Orthopaedic Surgery, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases The Third Affiliated Hospital of Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010jia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery Second Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010cheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Spinal Surgery Southern Medical University Nanfang Hospital  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong\u2010ping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Orthopaedic Surgery, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases The Third Affiliated Hospital of Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010chun","family":"Bai","sequence":"additional","affiliation":[{"name":"Center for Orthopaedic Surgery, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases The Third Affiliated Hospital of Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping\u2010lin","family":"Lai","sequence":"additional","affiliation":[{"name":"Center for Orthopaedic Surgery, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases The Third Affiliated Hospital of Southern Medical University  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