F-spondin regulates chondrocyte terminal differentiation and endochondral bone formation

J Orthop Res. 2010 Oct;28(10):1323-9. doi: 10.1002/jor.21130.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Chick Embryo
  • Chondrocytes / cytology*
  • Chondrocytes / drug effects
  • Chondrocytes / physiology
  • Extracellular Matrix Proteins / physiology*
  • Female
  • Growth Plate / cytology
  • Growth Plate / physiology
  • Matrix Metalloproteinase 13 / metabolism
  • Mice
  • Mice, Inbred Strains
  • Models, Animal
  • Osteogenesis / physiology*
  • Pregnancy
  • Transforming Growth Factor beta / pharmacology
  • Tretinoin / pharmacology


  • Extracellular Matrix Proteins
  • F-spondin protein, mouse
  • Transforming Growth Factor beta
  • Tretinoin
  • Alkaline Phosphatase
  • Matrix Metalloproteinase 13