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Mesenchymal stem cells (MSCs) within their native environment receive biochemical stimuli from surrounding cells that influences their differentiation into bone precursors, while the roles of osteocytes in regulating the osteogenic differentiation of MSCs remain unclear. This study investigated the specific roles of IL\u201017 signaling cascades and osteocyte\u2010specific pathways in the osteogenesis of MSCs. Using a transwell coculture (CC) system, we explored the effects of osteocytes and osteoblasts on the osteogenesis of MSCs with and without IL\u201017 supplementation. A polycaprolactone (PCL) three\u2010dimensional (3D) culture model was used to evaluate their osteogenic potential in the presence of osteocytes and IL\u201017. Notably, IL\u201017 induced osteogenesis in MSCs, which could be attenuated by blocking IL\u201017 receptor A. The osteogenic differentiation of MSCs promoted by IL\u201017 was further enhanced by CC with osteocytes. Moreover, proinflammatory cytokines IL\u20106 and IL\u20101\u03b2 played an important role in IL\u201017\u2010dependent differentiation, via the phosphorylation of AKT, signal transducer and activator of transcription 3, and extracellular signal\u2010regulated kinase 1\/2 signaling pathways in the MSC niche. The present study confirms a synergistic effect of osteocytes and IL\u201017 in the production of biochemical signals to stimulate the osteogenic differentiation of MSCs, which could be further promoted in the PCL 3D\u2010scaffold. These findings provide important insight into the mechanisms of MSCs activation and osteogenic differentiation within the native stem cell niche, and suggest a possible role of IL\u201017 in bone tissue engineering.<\/jats:p>","DOI":"10.1002\/jcp.29323","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T19:10:29Z","timestamp":1571857829000},"page":"4466-4480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["IL\u201017 alters the mesenchymal stem cell niche towards osteogenesis in cooperation with osteocytes"],"prefix":"10.1002","volume":"235","author":[{"given":"Chongshan","family":"Liao","sequence":"first","affiliation":[{"name":"Orthodontics, School of Stomatology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration Tongji University Shanghai China"},{"name":"Faculty of Dentistry The University of Hong Kong Sai Ying Pun Hong Kong 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