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Notably, we found that intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and osteoprotegerin (OPG) play a synergistic role in SSC-mediated suppression of inflammatory osteoclastogenesis. The effect of SSCs on inflammatory osteoclastogenesis was investigated using a lipopolysaccharide-induced mouse osteolysis model in vivo and human osteoarthritis synovial fluid (OASF) in vitro. OC formation was determined by tartrate-resistant acid phosphatase staining. Bone resorption was evaluated by microcomputerized tomography, serum C-terminal telopeptide assay, and pit formation assay. The expression of ICAM-1, VCAM-1, and OPG in SSCs and their contribution to the suppression of osteoclastogenesis were determined by flow cytometry or enzyme linked immunosorbent assay. Gene modification, neutralization antibodies, and tumor necrosis factor-\u03b1 knockout mice were used to further explore the mechanism. The results demonstrated that SSCs remarkably inhibited inflammatory osteoclastogenesis in vivo and in vitro. Mechanistically, inflammatory OASF stimulated ICAM-1 and VCAM-1 expression as well as OPG secretion by SSCs. In addition, ICAM-1 and VCAM-1 recruited CD11b+ OC progenitors to proximity with SSCs, which strengthened the inhibitory effects of SSC-derived OPG on osteoclastogenesis. Furthermore, it was revealed that tumor necrosis factor \u03b1 is closely involved in the suppressive effects. In summary, SSCs express a higher level of ICAM-1 and VCAM-1 and produce more OPG in inflammatory microenvironments, which are sufficient to inhibit osteoclastogenesis in a \u201ccapture and educate\u201d manner. These results may represent a synergistic mechanism to prevent bone erosion during joint inflammation by SSCs.<\/jats:p>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Significance Statement Skeletal stem cells (SSCs), tissue-specific stem cells from the skeleton, have been highlighted in recent scientific research and translational medicine. Although SSCs have been shown to contribute to skeletal development and regeneration, the regulation in osteoclastogenesis, the bone remodeling, and the application potential of SSCs in inflammatory bone diseases are incompletely understood. This study indicates a population of murine long-bone-derived SSCs have the potential to induce the expression of OPG, as well as ICAM-1 and VCAM-1 under inflammatory microenvironments and suppressed inflammatory osteoclast formation and bone resorption in vivo and in vitro. These findings indicate the possibility of using SSCs to alleviate bone loss in diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/sctm.19-0300","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T15:03:43Z","timestamp":1574867023000},"page":"261-272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Skeletal stem cell-mediated suppression on inflammatory osteoclastogenesis occurs via concerted action of cell adhesion molecules and osteoprotegerin"],"prefix":"10.1093","volume":"9","author":[{"given":"Xin","family":"Li","sequence":"first","affiliation":[{"name":"1 Beijing Institute of Radiation Medicine, Beijing, People's Republic of China"},{"name":"2 Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China"},{"name":"3 Air Force Medical Center, PLA, Beijing, People's Republic of China"},{"name":"4 Jizhong Energy Xingtai MIG General Hospital, Xingtai, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Ding","sequence":"additional","affiliation":[{"name":"1 Beijing Institute of Radiation Medicine, Beijing, People's Republic of China"},{"name":"3 Air Force Medical Center, PLA, Beijing, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Xing","family":"Wang","sequence":"additional","affiliation":[{"name":"1 Beijing Institute of Radiation Medicine, Beijing, People's Republic of China"},{"name":"5 People's Liberation Army General Hospital, Beijing, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong-Li","family":"Li","sequence":"additional","affiliation":[{"name":"5 People's Liberation Army General Hospital, Beijing, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"1 Beijing 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