{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:43:17Z","timestamp":1791110597176,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1105403"],"award-info":[{"award-number":["2022YFA1105403"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021A1515110916"],"award-info":[{"award-number":["2021A1515110916"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2022YFA1105403"],"award-info":[{"award-number":["2022YFA1105403"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515110916"],"award-info":[{"award-number":["2021A1515110916"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoclastogenesis is tightly regulated by receptor activator of nuclear factor kappa-B ligand (RANKL) signaling, yet the role of matrix metalloproteinase-9 (MMP-9) in this process remains controversial. We established a high-yield osteoclastogenesis system using cryopreserved rabbit bone marrow cells (1 \u00d7 109 cells\/femur) treated with Macrophage colony-stimulating factor (M-CSF) and RANKL. Bone marrow cells from MMP-9 transgenic rabbits (macrophage-specific overexpression) and MMP-9-transfected RAW264.7 macrophages were compared to wild-type controls. MMP-9 overexpression increased osteoclastogenesis 5.5-fold (20 ng\/mL RANKL, * p &lt; 0.01) while suppressing inflammatory cytokines (IL-1\u03b2, TNF-\u03b1). RAW264.7 macrophages stably transfected with human MMP-9 similarly exhibited reduced inflammatory cytokine levels and enhanced osteoclastogenesis. MMP-9 acts as a dual regulator of osteoclastogenesis and inflammation, suggesting therapeutic potential for osteoporosis management.<\/jats:p>","DOI":"10.3390\/ijms26073194","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T03:25:02Z","timestamp":1743391502000},"page":"3194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Matrix Metalloproteinase-9 Enhances Osteoclastogenesis: Insights from Transgenic Rabbit Bone Marrow Models and In Vitro Studies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6567-0396","authenticated-orcid":false,"given":"Yajie","family":"Chen","sequence":"first","affiliation":[{"name":"Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China"},{"name":"Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialun","family":"Zou","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3694-5642","authenticated-orcid":false,"given":"Manabu","family":"Niimi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5237-1927","authenticated-orcid":false,"given":"Xuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maobi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1737-6130","authenticated-orcid":false,"given":"Jianglin","family":"Fan","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China"},{"name":"Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_2","first-page":"65","article-title":"Osteoclast formation and differentiation: An overview","volume":"59","author":"Soysa","year":"2012","journal-title":"J. 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