Collaborative action of M-CSF and CTGF/CCN2 in articular chondrocytes: Possible regenerative roles in articular cartilage metabolism

Kyouji Nakao, Satoshi Kubota, Hideyuki Doi, Takanori Eguchi, Morihiko Oka, Takuo Fujisawa, Takashi Nishida, Masaharu Takigawa

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

It is known that expression of the macrophage colony-stimulating factor (M-CSF) gene is induced in articular chondrocytes upon inflammation. However, the functional role of M-CSF in cartilage has been unclear. In this study, we describe possible roles of M-CSF in the protection and maintenance of the articular cartilage based on the results of experiments using human chondrocytic cells and rat primary chondrocytes. Connective tissue growth factor (CTGF/CCN2) is known to be a potent molecule to regenerate damaged cartilage by promoting the growth and differentiation of articular chondrocytes. Here, we uncovered the fact that M-CSF induced the mRNA expression of the ctgf/ccn2 gene in those cells. Enhanced production of CTGF/CCN2 protein by M-CSF was also confirmed. Furthermore, M-CSF could autoactivate the m-csf gene, forming a positive feed-back network to amplify and prolong the observed effects. Finally, promotion of proteoglycan synthesis was observed by the addition of M-CSF. These findings taken together indicate novel roles of M-CSF in articular cartilage metabolism in collaboration with CTGF/CCN2, particularly during an inflammatory response. Such roles of M-CSF were further supported by the distribution of M-CSF producing chondrocytes in experimentally induced rat osteoarthritis cartilage in vivo.

Original languageEnglish
Pages (from-to)884-892
Number of pages9
JournalBone
Volume36
Issue number5
DOIs
Publication statusPublished - May 2005

Keywords

  • CCN family
  • Chondrocytes
  • Connective tissue growth factor (CTGF)
  • M-CSF
  • Regeneration

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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