Title

F-Spondin Regulates Chondrocyte Terminal Differentiation and Endochondral Bone Formation

Document Type

Article

Publication Date

10-1-2010

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.

Publication Title

Journal of Orthopaedic Research

Volume

28

Issue

10

First Page

1323

Last Page

1329

PubMed ID

20839318

Comments

This article was published in Journal of Orthopaedic Research, Volume 28, Issue 10, October 2010, Pages 1323-9.

The published version is available at http://dx.doi.org/10.1002/jor.21130

Copyright © 2010 Orthopaedic Research Society

This document is currently not available here.

COinS