Collaborative action of M-CSF and CTGF/CCN2 in articular chondrocytes: possible regenerative roles in articular cartilage metabolism.
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.
Nakao
Kyouji
K
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
Kubota
Satoshi
S
Doi
Hideyuki
H
Eguchi
Takanori
T
Oka
Morihiko
M
Fujisawa
Takuo
T
Nishida
Takashi
T
Takigawa
Masaharu
M
D001483:Base Sequence; D002358:Cartilage, Articular / Q000502:physiology*; D002460:Cell Line; D019902:Chondrocytes / Q000502:physiology*; D055513:Connective Tissue Growth Factor; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010003:Osteoarthritis / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism
C526317:CCN2 protein, human; C526316:CCN2 protein, rat; D017931:DNA Primers; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D055513:Connective Tissue Growth Factor; D016173:Macrophage Colony-Stimulating Factor