Galectin-3 is a downstream regulator of matrix metalloproteinase-9 function during endochondral bone formation.
Endochondral bone formation is characterized by the progressive replacement of a cartilage anlagen by bone at the growth plate with a tight balance between the rates of chondrocyte proliferation, differentiation, and cell death. Deficiency of matrix metalloproteinase-9 (MMP-9) leads to an accumulation of late hypertrophic chondrocytes. We found that galectin-3, an in vitro substrate of MMP-9, accumulates in the late hypertrophic chondrocytes and their surrounding extracellular matrix in the expanded hypertrophic cartilage zone. Treatment of wild-type embryonic metatarsals in culture with full-length galectin-3, but not galectin-3 cleaved by MMP-9, mimicked the embryonic phenotype of Mmp-9 null mice, with an increased hypertrophic zone and decreased osteoclast recruitment. These results indicate that extracellular galectin-3 could be an endogenous substrate of MMP-9 that acts downstream to regulate hypertrophic chondrocyte death and osteoclast recruitment during endochondral bone formation. Thus, the disruption of growth plate homeostasis in Mmp-9 null mice links galectin-3 and MMP-9 in the regulation of the clearance of late chondrocytes through regulation of their terminal differentiation.
Ortega
Nathalie
N
Department of Anatomy, University of California-San Francisco, San Francisco, CA 94143, USA.
Behonick
Danielle J
DJ
Colnot
Céline
C
Cooper
Douglas N W
DN
Werb
Zena
Z
D000818:Animals; D015153:Blotting, Western; D001846:Bone Development; D001842:Bone and Bones / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism*; D006132:Growth Plate / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D006811:Humerus / Q000166:cytology / Q000196:embryology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008682:Metatarsal Bones / Q000166:cytology / Q000196:embryology; D051379:Mice; D008817:Mice, Mutant Strains; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism
D037502:Galectin 3; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9