title: Role of interleukin-10 in endochondral bone formation in mice: anabolic effect via the bone morphogenetic protein/Smad pathway.
abstract: OBJECTIVE
  Interleukin-10 (IL-10) is a pleiotropic immunoregulatory cytokine with a chondroprotective effect that is elevated in cartilage and synovium in patients with osteoarthritis. However, the role of IL-10 during endochondral bone formation and its mechanism of action have not been elucidated.
  
  
  METHODS
  IL-10(-/-) mice and IL-10-treated tibial organ cultures were used to study loss and gain of IL-10 functions, respectively, during endochondral bone formation. Primary chondrocytes from the long bones of mouse embryos were cultured with and without IL-10. To assess the role of IL-10 in chondrogenic differentiation, we conducted mesenchymal cell micromass cultures.
  
  
  RESULTS
  The lengths of whole skeletons from IL-10(-/-) mice were similar to those of their wild-type littermates, although their skull diameters were smaller. The tibial growth plates of IL-10(-/-) mice showed shortening of the proliferating zone. Treatment with IL-10 significantly increased tibial lengths in organ culture. IL-10 also induced chondrocyte proliferation and hypertrophic differentiation in primary chondrocytes in vitro. Mechanistically, IL-10 activated STAT-3 and the Smad1/5/8 and ERK-1/2 MAP kinase pathways and induced the expression of bone morphogenetic protein 2 (BMP-2) and BMP-6 in primary chondrocytes. Furthermore, the blocking of BMP signaling attenuated the IL-10-mediated induction of cyclin D1 and RUNX-2 in primary chondrocytes and suppressed Alcian blue and alkaline phosphatase staining in mesenchymal cell micromass cultures.
  
  
  CONCLUSIONS
  These results indicate that IL-10 acts as a stimulator of chondrocyte proliferation and chondrogenic or hypertrophic differentiation via activation of the BMP signaling pathway.
authors.affiliation: Fatima Research Institute and Daegu Fatima Hospital, Daegu, Republic of Korea.
authors.forename: Youn-Kwan
authors.initials: YK
authors.lastname: Jung
authors.forename: Gun-Woo
authors.initials: GW
authors.lastname: Kim
authors.forename: Hye-Ri
authors.initials: HR
authors.lastname: Park
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
authors.forename: Frank
authors.initials: F
authors.lastname: Beier
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Han
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051785:Smad Proteins / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D051785:Smad Proteins; D016753:Interleukin-10