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Authordc.contributor.authorLu, Laura 
Authordc.contributor.authorLoi, Florence 
Authordc.contributor.authorNathan, Karthik 
Authordc.contributor.authorLin, Tzu 
Authordc.contributor.authorPajarinen, Jukka 
Authordc.contributor.authorGibon, Emmanuel 
Authordc.contributor.authorNabeshima, Akira 
Authordc.contributor.authorCordova, Luis 
Authordc.contributor.authorJämsen, Eemeli 
Authordc.contributor.authorYao, Zhenyu 
Authordc.contributor.authorGoodman, Stuart 
Cita de ítemdc.identifier.citationJournal of Orthopaedic Research, Volumen 35, Issue 11, 2017, Pages 2378-2385.
Abstractdc.description.abstractBone fractures are among the most common orthopaedic problems that affect individuals of all ages. Immediately after injury, activated macrophages dynamically contribute to and regulate an acute inflammatory response that involves other cells at the injury site, including mesenchymal stem cells (MSCs). These macrophages and MSCs work in concert to modulate bone healing. In this study, we co-cultured undifferentiated M0, pro-inflammatory M1, and anti-inflammatory M2 macrophages with primary murine MSCs in vitro to determine the cross-talk between polarized macrophages and MSCs and their effects on osteogenesis. After 4 weeks of coculture, MSCs grown with macrophages, especially M1 macrophages, had enhanced bone mineralization compared to MSCs grown alone. The level of bone formation after 4 weeks of culture was closely associated with prostaglandin E2 (PGE2) secretion early in osteogenesis. Treatment with celecoxib, a cyclooxygenase-2 (COX-2) selective inhibitor, significantly reduced bone mineralization in all co-cultures but most dramatically in the M1-MSC co-culture. We also found that the presence of macrophages reduced the secretion of osteoprotegerin (OPG), the decoy RANKL receptor, suggesting that macrophages may indirectly modulate osteoclast activity in addition to enhancing bone formation. Taken together, these findings suggest that an initial pro-inflammatory phase modulated by M1 macrophages promotes osteogenesis in MSCs via the COX-2-PGE2 pathway. Understanding the complex interactions between macrophages and MSCs provide opportunities to optimize bone healing and other regenerative processes via modulation of the inflammatory response. This study provides one possible biological mechanism for the adverse effects of non-steroidal antiinflammatory drugs on fracture healing and bone regeneration.
Publisherdc.publisherJohn Wiley and Sons Inc.
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
Link to Licensedc.rights.uri
Sourcedc.sourceJournal of Orthopaedic Research
Keywordsdc.subjectFracture healing
Keywordsdc.subjectMesenchymal stem cells
Keywordsdc.subjectPolarized macrophages
Títulodc.titlePro-inflammatory M1 macrophages promote Osteogenesis by mesenchymal stem cells via the COX-2-prostaglandin E2 pathway
Document typedc.typeArtículo de revista
Indexationuchile.indexArtículo de publicación SCOPUS

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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile