{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T17:27:13Z","timestamp":1786814833772,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,7,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    17\u03b2\u2010estradiol is a potent endogenous estrogen used for postmenopausal osteoporosis treatment. Its osteoprotective role correlates with matrix metalloproteinase (MMP) and mitochondrial homeostasis. This research sought to examine the role of 17\u03b2\u2010estradiol on MMP\u20108 in mitochondrial homeostasis and elucidate the potential regulatory pathways. We evaluated the effects of 17\u03b2\u2010estradiol on MMP\u20108, bone loss, osteogenic differentiation, and mitochondrial homeostasis in bilateral ovariectomy (OVX)\u2010induced mice and MC3T3\u2010E1 cells. MMP\u20108 was overexpressed to validate its regulatory relationship with 17\u03b2\u2010estradiol. Comprehensive analyses were further conducted to identify the potential pathways associated with MMP\u20108. The Ras pathway agonist ML\u2010099 and inhibitor Lonafarnib were used for pathway validation. 17\u03b2\u2010estradiol treatment attenuated bone loss and increased osteogenic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , osteoprotegerin (OPG), and osteocalcin (OC) levels. It inhibited reactive oxygen species (ROS) and malondialdehyde (MDA), promoted superoxide dismutase (SOD) activity, and restored mitochondrial homeostasis via upregulating the expression of dynamin\u2010related protein 1 (DRP1), mitofusin 1 (MFN1), and peroxisome proliferator\u2010activated receptor \u03b3 coactivator 1 alpha (PGC\u20101\u03b1), accompanied by increased adenosine triphosphate (ATP), mitochondrial membrane potential, and mitochondrial oxygen consumption. MMP\u20108 overexpression significantly reversed these protective effects. The Ras pathway was identified as a potential pathway associated with MMP\u20108\u2010mediated osteoporosis regulation. ML\u2010099 administration in 17\u03b2\u2010estradiol + MMP\u20108 overexpression cells markedly restored mitochondrial homeostasis and rescued osteogenic differentiation. Conversely, the adverse impacts of MMP\u20108 overexpression on osteoblast differentiation, mitochondrial homeostasis, and Ras activation were further aggravated by Lonafarnib treatment. 17\u03b2\u2010estradiol maintains mitochondrial homeostasis in osteoblasts via inhibiting MMP\u20108 and activating the Ras pathway, which provides novel potential targets for postmenopausal osteoporosis management.\n                  <\/jats:p>","DOI":"10.1096\/fj.202601404r","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:31:16Z","timestamp":1784734276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["17\u03b2\u2010Estradiol Maintains Mitochondrial Homeostasis in Osteoblasts by Inhibiting\n                    <scp>MMP<\/scp>\n                    \u20108 and Activating the Ras Signaling Pathway in Postmenopausal Osteoporosis"],"prefix":"10.1096","volume":"40","author":[{"given":"Huan","family":"Min","sequence":"first","affiliation":[{"name":"Department of Orthopedics Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabin","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics 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