F-spondin, a neuroregulatory protein, is up-regulated in osteoarthritis and regulates cartilage metabolism via TGF-β activation

Mukundan G. Attur, Glyn D. Palmer, Hayf E. Al-Mussawir, Mandar Dave, Cristina Teixeira, Daniel B. Rifkin, C. Thomas G Appleton, Frank Beier, Steven B. Abramson

Research output: Contribution to journalArticle

Abstract

In osteoarthritis (OA) articular chondrocytes undergo phenotypic changes culminating in the progressive loss of cartilage from the joint surface. The molecular mechanisms underlying these changes are poorly understood. Here we report enhanced (∼7-fold) expression of F-spondin, a neuronal extracellular matrix glycoprotein, in human OA cartilage (P<0.005). OA-specific up-regulation of F-spondin was also demonstrated in rat knee cartilage following surgical menisectomy. F-spondin treatment of OA cartilage explants caused a 2-fold increase in levels of the active form of TGF-β1 (P<0.01) and a 10-fold induction of PGE2 (P<0.005) in culture supernatants. PGE2 induction was found to be dependent on TGF-β and the thrombospondin domain of the F-spondin molecule. F-spondin addition to cartilage explant cultures also caused a 4-fold increase in collagen degradation (P<0.05) and a modest reduction in proteoglycan synthesis (∼20%; P<0.05), which were both TGF-β and PGE2 dependent. F-spondin treatment also led to increased secretion and activation of MMP-13 (P<0.05). Together these studies identify F-spondin as a novel protein in OA cartilage, where it may act in situ at lesional areas to activate latent TGF-β and induce cartilage degradation via pathways that involve production of PGE2.

Original languageEnglish (US)
Pages (from-to)79-89
Number of pages11
JournalFASEB Journal
Volume23
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Cartilage
Metabolism
Osteoarthritis
Chemical activation
Dinoprostone
Proteins
Joints
Thrombospondins
Degradation
Proteoglycans
Chondrocytes
Matrix Metalloproteinases
Extracellular Matrix
Rats
Knee
Glycoproteins
Up-Regulation
Collagen
Molecules

Keywords

  • Chondrocyte regulation
  • Extracellular matrix
  • Prostaglandin

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

F-spondin, a neuroregulatory protein, is up-regulated in osteoarthritis and regulates cartilage metabolism via TGF-β activation. / Attur, Mukundan G.; Palmer, Glyn D.; Al-Mussawir, Hayf E.; Dave, Mandar; Teixeira, Cristina; Rifkin, Daniel B.; Appleton, C. Thomas G; Beier, Frank; Abramson, Steven B.

In: FASEB Journal, Vol. 23, No. 1, 01.2009, p. 79-89.

Research output: Contribution to journalArticle

Attur, MG, Palmer, GD, Al-Mussawir, HE, Dave, M, Teixeira, C, Rifkin, DB, Appleton, CTG, Beier, F & Abramson, SB 2009, 'F-spondin, a neuroregulatory protein, is up-regulated in osteoarthritis and regulates cartilage metabolism via TGF-β activation', FASEB Journal, vol. 23, no. 1, pp. 79-89. https://doi.org/10.1096/fj.08-114363
Attur, Mukundan G. ; Palmer, Glyn D. ; Al-Mussawir, Hayf E. ; Dave, Mandar ; Teixeira, Cristina ; Rifkin, Daniel B. ; Appleton, C. Thomas G ; Beier, Frank ; Abramson, Steven B. / F-spondin, a neuroregulatory protein, is up-regulated in osteoarthritis and regulates cartilage metabolism via TGF-β activation. In: FASEB Journal. 2009 ; Vol. 23, No. 1. pp. 79-89.
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