{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:47:32Z","timestamp":1787014052811,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T00:00:00Z","timestamp":1569542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["Grant NO. 81500686 and 81601230"],"award-info":[{"award-number":["Grant NO. 81500686 and 81601230"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Osteopetrosis is a rare inherited skeletal disease characterized by increased bone mineral density due to the loss of osteoclast function or differentiation potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      The study involved a Chinese patient with osteopetrosis (the proband) and her immediate family members and 180 controls without osteopetrosis. Bone density of the femoral neck, lumbar spine and total body was measured using dual\u2010energy x\u2010ray absorptiometry. Osteoclast differentiation by the participants\u2019 peripheral blood mononuclear cells (PBMCs) was investigated using tartrate\u2010resistant acid phosphatase (TRAP) staining. Osteoblast differentiation was examined with Alizarin Red S staining. Reverse transcription\u2010quantitative PCR was used to amplify immunoglobulin superfamily member 23 (\n                      <jats:italic>IGSF23<\/jats:italic>\n                      ), c\u2010\n                      <jats:italic>FOS<\/jats:italic>\n                      and nuclear factor of activated T cells 1 (NFATC1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found a homozygous mutation (c.295C&gt;T) in the\n                      <jats:italic>IGSF23<\/jats:italic>\n                      gene in two osteopetrosis samples. The mutation led to the formation of a stop codon, causing loss of the immunoglobulin\u2010like domain and the whole transmembrane domain. PBMCs from the proband (\n                      <jats:italic>IGSF23<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) exhibited poor ability for differentiating into mature osteoclasts in vitro. Overexpression of\n                      <jats:italic>IGSF23<\/jats:italic>\n                      rescued the ability of\n                      <jats:italic>IGSF23<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      PBMCs to differentiate into osteoclasts. Moreover, knockdown of IGSF23 reversed the bone loss in OVX mice by injecting AAV\u2010shIGSF23 into mice femoral bone marrow cavity. Furthermore, we also found that the\n                      <jats:italic>IGSF23<\/jats:italic>\n                      mutation led to decreased c\u2010Fos and NFATC1 expression levels by inhibiting the mitogen\u2010activated protein kinase signalling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IGSF23\u2010mediated osteoclast differentiation of PBMCs may serve as a potential target in osteoporosis therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cpr.12693","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T07:16:15Z","timestamp":1569568575000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Osteoclastogenesis inhibition by mutated IGSF23 results in human osteopetrosis"],"prefix":"10.1111","volume":"52","author":[{"given":"Ying","family":"Yuan","sequence":"first","affiliation":[{"name":"Institute of Endocrinology and Metabolism The Second Xiangya Hospital Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Hunan Provincial People's Hospital Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology and Metabolism The Second Xiangya Hospital Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology and Metabolism The Second Xiangya Hospital Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0126-4978","authenticated-orcid":false,"given":"Qiong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Xiangya Hospital Central South University Changsha Hunan 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