Stem Cells Translational Medicine (Feb 2020)

Skeletal stem cell‐mediated suppression on inflammatory osteoclastogenesis occurs via concerted action of cell adhesion molecules and osteoprotegerin

  • Xin Li,
  • Li Ding,
  • Yu‐Xing Wang,
  • Zhong‐Li Li,
  • Qian Wang,
  • Zhi‐Dong Zhao,
  • Sen Zhao,
  • Hua Wang,
  • Chu‐Tse Wu,
  • Ning Mao,
  • Heng Zhu

DOI
https://doi.org/10.1002/sctm.19-0300
Journal volume & issue
Vol. 9, no. 2
pp. 261 – 272

Abstract

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Abstract In the current study, we investigated how skeletal stem cells (SSCs) modulate inflammatory osteoclast (OC) formation and bone resorption. 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‐α 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 α 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 “capture and educate” manner. These results may represent a synergistic mechanism to prevent bone erosion during joint inflammation by SSCs.

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