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F-Spondin Regulates Chondrocyte Terminal Differentiation and Endochondral Bone Formation
Journal of Orthopaedic Research
  • Glyn D. Palmer
  • Alejandro H. Piton
  • Lwin Mon Thant
  • Serafim M. Oliveira
  • Marina D'Angelo, Philadelphia College of Osteopathic Medicine
  • Mukundan G. Attur
  • Steven B. Abramson
  • Cristina C. Teixeira
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This study examines the role of F-spondin, an extracellular matrix protein of osteoarthritic cartilage, during chondrocyte maturation in embryonic growth plate cartilage. In chick tibia, F-spondin expression localized to the hypertrophic and calcified zones of the growth plate. Functional studies using tibial organ cultures indicated that F-spondin inhibited (∼35%, p = 0.02), and antibodies to F-spondin increased (∼30%, p < 0.1) longitudinal limb growth relative to untreated controls. In cell cultures, induction of chondrocyte maturation, by retinoic acid (RA) or transforming growth factor (TGF)-β treatment led to a significant upregulation of F-spondin (p < 0.05). F-spondin transfection increased mineral deposition, alkaline phosphatase (AP) and matrix metalloproteinase (MMP)-13 mRNA levels (p < 0.05), and AP activity following RA stimulation, compared to mock transfected controls. Using AP as a differentiation marker we then investigated the mechanism of F-spondin promaturation effects. Blocking endogenous F-spondin via its thrombospondin (TSR) domain inhibited RA induced AP activity 40% compared to controls (p < 0.05). The stimulatory effect of F-spondin on AP expression was also inhibited following depletion of TGF-β from culture supernatants. Our findings indicate that F-spondin is expressed in embryonic cartilage, where it has the capacity to enhance chondrocyte terminal differentiation and mineralization via interactions in its TSR domain and TGF-β dependent pathways.
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This article was published in Journal of Orthopaedic Research, Volume 28, Issue 10, October 2010, Pages 1323-9.

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Copyright © 2010 Orthopaedic Research Society

Citation Information
Glyn D. Palmer, Alejandro H. Piton, Lwin Mon Thant, Serafim M. Oliveira, et al.. "F-Spondin Regulates Chondrocyte Terminal Differentiation and Endochondral Bone Formation" Journal of Orthopaedic Research Vol. 28 Iss. 10 (2010) p. 1323 - 1329
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