F-spondin regulates chondrocyte terminal differentiation and endochondral bone formation

Glyn D. Palmer, Alejandro H. Piton, Lwin Mon Thant, Serafim M. Oliveira, Marina D'Angelo, Mukundan G. Attur, Steven B. Abramson, Cristina C. Teixeira

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1323-1329
Number of pages7
JournalJournal of Orthopaedic Research
Volume28
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • Chondrocyte maturation
  • Growth plate
  • Hypertrophy
  • Transforming growth factor (TGF)-β

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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    Palmer, G. D., Piton, A. H., Thant, L. M., Oliveira, S. M., D'Angelo, M., Attur, M. G., Abramson, S. B., & Teixeira, C. C. (2010). F-spondin regulates chondrocyte terminal differentiation and endochondral bone formation. Journal of Orthopaedic Research, 28(10), 1323-1329. https://doi.org/10.1002/jor.21130