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PMID:15800063
| Citation |
Ortega, N, Behonick, DJ, Colnot, C, Cooper, DN and Werb, Z (2005) Galectin-3 is a downstream regulator of matrix metalloproteinase-9 function during endochondral bone formation. Mol. Biol. Cell 16:3028-39 |
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| Abstract |
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. |
| Links |
PubMed PMC1142445 Online version:10.1091/mbc.E04-12-1119 |
| Keywords |
Animals; Antigens, CD31/metabolism; Blotting, Western; Bone Development; Bone and Bones/cytology; Bone and Bones/enzymology; Bone and Bones/metabolism; Cell Differentiation; Cells, Cultured; Chondrocytes/metabolism; Extracellular Matrix/metabolism; Galectin 3/metabolism; Growth Plate/cytology; Growth Plate/embryology; Growth Plate/growth & development; Growth Plate/metabolism; Humerus/cytology; Humerus/embryology; Immunohistochemistry; In Situ Hybridization; Matrix Metalloproteinase 9/metabolism; Metatarsal Bones/cytology; Metatarsal Bones/embryology; Mice; Mice, Mutant Strains |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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