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Oversulfated chondroitin sulfate‐E binds to BMP‐4 and enhances osteoblast differentiation
Author(s) -
Miyazaki Tatsuya,
Miyauchi Satoshi,
Tawada Akira,
Anada Takahisa,
Matsuzaka Satoshi,
Suzuki Osamu
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21557
Subject(s) - mineralization (soil science) , chemistry , chondroitin sulfate , osteoblast , alkaline phosphatase , glycosaminoglycan , biochemistry , bone morphogenetic protein 2 , sulfation , heparin , proteoglycan , microbiology and biotechnology , biology , in vitro , enzyme , extracellular matrix , organic chemistry , nitrogen
Small leucine‐rich proteoglycans, such as biglycan, and their side chain sulfated glycosaminoglycans (GAGs), have been suggested to be involved in bone formation and mineralization processes. The present study was designed to investigate whether chondroitin sulfate (CS), one of the GAG, and its oversulfated structures coupled with bone morphogenetic protein‐4 (BMP‐4) alter the differentiation and subsequent mineralization of MC3T3‐E1 osteoblastic cells. CS‐E, one of the oversulfated CS structure, enhanced cell growth, alkaline phosphatase (ALP) activity, collagen deposition, and mineralization whereas heparin enhanced only ALP activity and mineralization. As well as CS‐E, CS‐H, and CPS also enhanced the mineralization of the cells. CS‐E enhanced the mineralization of the cells by interacting with protein in the conditioned medium. CS‐E induced mineralization was significantly inhibited by an antibody against BMP‐4. The addition of exogenous BMP‐4 further increased the capacity of CS‐E to enhance mineralization. Fluorescence correlation spectroscopy method using fluoresceinamine‐labeled GAG revealed that the oversulfated GAGs have a high affinity for BMP‐4. The disaccharide analysis of the cells indicated that MC3T3‐E1 cells are capable of producing oversulfated structures of CS by themselves. The lack of CS from the cells after chondroitinase treatment resulted in the inhibition of mineralization. These results in the present study indicate that oversulfated CS, which possesses 4,6‐disulfates in N ‐acetyl‐galactosamine, binds to BMP‐4 and promotes osteoblast differentiation and subsequent mineralization. J. Cell. Physiol. 217: 769–777, 2008. © 2008 Wiley‐Liss, Inc.