Lysyl oxidase regulates transforming growth factor-ß1 function in bone

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  • March 21, 2019
Creator
  • Atsawasuwan, Phimon
    • Affiliation: School of Dentistry, Oral Biology PhD Program
Abstract
  • Lysyl oxidase (LOX), an amine oxidase critical for the initiation of collagen and elastin cross-linking, has recently been shown to regulate cellular activities possibly by modulating growth factor activity. In this study, we discovered that osteoblastic (MC3T3-E1) cell-derived clones expressing higher (S) levels of LOX exhibited smaller collagen fibrils and lower collagen production than controls (MC, EV) while the clones expressing lower (AS) levels of LOX exhibited larger collagen fibrils and higher amount of collagen leading to subsequent defective mineralization. In order to elucidate the mechanisms by which collagen synthesis is controlled through LOX, we investigated the potential role of LOX in regulating growth factors. We further investigated the interaction of LOX with TGF-ß1, a potent growth factor abundant in bone, and evaluated the effect of this interaction. The specific binding between LOX and TGF-ß1 was demonstrated both by immunoprecipitation and glutathione-S-transferase pull down assay. Both molecules were co-localized in the extracellular matrix in culture and the binding complex was identified in the mineral-associated fraction of bone matrix. Furthermore, LOX suppressed TGF-ß1 induced Smad3 phosphorylation and collagen (I/V) expression but the effects were nullified by ß-aminopropionitrile. The suppression of Smad3 phosphorylation was not affected by the presence of catalase. The data indicate that LOX may bind to mature TGF-ß1 and regulate its signaling via its amine oxidase activity in bone, thus, may play an important role in bone remodeling and mineralization.
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  • In Copyright
Advisor
  • Yamauchi, Mitsuo
Degree granting institution
  • University of North Carolina at Chapel Hill
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