{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:29:15Z","timestamp":1779377355981,"version":"3.53.1"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008108","name":"Taipei Tzu Chi Hospital","doi-asserted-by":"crossref","award":["TCRD-TPE-112-27"],"award-info":[{"award-number":["TCRD-TPE-112-27"]}],"id":[{"id":"10.13039\/501100008108","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity is a recognized risk factor for intervertebral disc (IVD) degeneration, a condition characterized by the progressive loss of extracellular matrix components in the nucleus pulposus. Elevated circulating leptin levels in obese individuals contribute to this degeneration by upregulating matrix metalloproteinase-1 (MMP-1) expression. Targeting MMP-1 expression with low-toxicity natural compounds may provide a promising strategy to prevent or mitigate IVD degeneration. In this study, we examined the effects of cinnamaldehyde (CA), a natural compound derived from Cinnamomum osmophloeum Kaneh, on leptin-induced MMP-1 expression in human IVD cartilage endplate-derived stem cells (SV40 cell line). Our results showed that leptin induced MMP-1 expression via activation of leptin receptor-mediated JAK2\/STAT3, JAK2\/RhoA\/STAT3, and RhoA\/ERK1\/2\/NF-\u03baB signaling pathways. CA significantly reduced MMP-1 expression by inhibiting phosphorylation of the leptin receptor and STAT3 and blocking RhoA and NF-\u03baB activation, without affecting JAK2 and ERK1\/2 phosphorylation. These findings suggest that CA suppresses leptin-induced MMP-1 expression by modulating specific signaling pathways, highlighting its potential as a therapeutic agent for IVD degeneration associated with obesity.<\/jats:p>","DOI":"10.3390\/ijms26199819","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:16Z","timestamp":1760107816000},"page":"9819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cinnamaldehyde Inhibits Leptin-Induced MMP-1 by Modulating Leptin Receptor\/STAT3 and Blocking RhoA\/NF-\u03baB Pathways in Human Intervertebral Disc Stem Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8436-8299","authenticated-orcid":false,"given":"Kuo-Feng","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Animal Science, National Ilan University, Ilan 260007, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Chiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsien-Ta","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"},{"name":"School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41413-020-00125-x","article-title":"Painful intervertebral disc degeneration and inflammation: From laboratory evidence to clinical interventions","volume":"9","author":"Lyu","year":"2021","journal-title":"Bone Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ohnishi, T., Iwasaki, N., and Sudo, H. 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