{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:19:22Z","timestamp":1790785162701,"version":"4.1.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is increasingly recognized as a low-grade inflammatory disease, yet how the inflammatory milieu interacts with regenerative signals remains poorly understood. Bone morphogenetic protein 2 (BMP-2) typically functions as an anabolic factor for cartilage; however, its levels are paradoxically elevated in degenerating joints. This study investigates whether the inflammatory microenvironment acts as a molecular switch that alters the functional outcome of BMP-2 signaling from repair to pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      BMP-2 levels were quantified in human OA cartilage and synovial fluid via immunofluorescence and ELISA, and correlated with radiographic severity (Kellgren-Lawrence grade). To model the inflammatory niche, ATDC5 chondrocytes and bone marrow\u2013derived mesenchymal stem cells (BMSCs) were co-stimulated with BMP-2 and Interleukin-1 beta (IL-1\u03b2).\n                      <jats:italic>In vivo<\/jats:italic>\n                      , a murine OA model was induced by destabilization of the medial meniscus (DMM), followed by intra-articular delivery of adenoviral vectors encoding BMP-2 and\/or IL-1\u03b2 to assess joint pathology and osteophyte formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinical analysis revealed that BMP-2 expression is significantly upregulated in OA tissues and correlates positively with disease severity. Mechanistically, IL-1\u03b2 stimulation induced endogenous BMP-2 expression in chondrocytes but blocked its chondrogenic effects, instead promoting hypertrophy. Crucially, the combination of BMP-2 and IL-1\u03b2 synergistically amplified osteogenic differentiation in BMSCs, as evidenced by robust upregulation of\n                      <jats:italic>Runx2<\/jats:italic>\n                      ,\n                      <jats:italic>OPN<\/jats:italic>\n                      , and\n                      <jats:italic>OCN<\/jats:italic>\n                      .\n                      <jats:italic>In vivo<\/jats:italic>\n                      , while BMP-2 alone showed mild protective effects, its presence in an IL-1\u03b2-rich environment severely exacerbated joint destruction and triggered massive osteophyte formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inflammation fundamentally repurposes BMP-2 signaling in the OA joint. Instead of promoting homeostasis, the synergy between BMP-2 and inflammatory cytokines drives mesenchymal progenitors toward pathological ossification. These findings highlight the critical role of the inflammatory microenvironment in specific OA phenotypes in dictating tissue fate and suggest that targeting this inflammatory switch is essential for effective OA therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1776833","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:36:19Z","timestamp":1774416979000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The inflammatory microenvironment repurposes BMP-2 signaling to drive pathological osteophyte formation in osteoarthritis"],"prefix":"10.3389","volume":"17","author":[{"given":"Chao","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, The University-Town Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Medical Sciences Research Center, University-Town Hospital of Chongqing 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