Cartilage abnormalities are associated with abnormal Phex expression and with altered matrix protein and MMP-9 localization in Hyp mice
| Autor: | Dengshun Miao, Dibyendu K. Panda, Marc D. McKee, Xiuying Bai, Andrew C. Karaplis, David Goltzman |
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| Rok vydání: | 2004 |
| Předmět: |
Bone sialoprotein
medicine.medical_specialty Histology Physiology Endocrinology Diabetes and Metabolism Osteocalcin Apoptosis Cartilage metabolism Gene mutation Bone and Bones Chondrocyte Mice Calcification Physiologic Chondrocytes Osteoclast Internal medicine medicine Animals Hypophosphatemia Familial Extracellular Matrix Proteins biology Chemistry Cartilage PHEX Proteins Hyperostosis Immunohistochemistry PHEX Phosphate Regulating Neutral Endopeptidase medicine.anatomical_structure Endocrinology Gene Expression Regulation Matrix Metalloproteinase 9 biology.protein Osteonectin |
| Zdroj: | Bone. 34:638-647 |
| ISSN: | 8756-3282 |
| DOI: | 10.1016/j.bone.2003.12.015 |
| Popis: | X-linked hypophosphatemic rickets (HYP) in humans is caused by mutations in the PHEX gene. This gene mutation is also found in Hyp mice, the murine homologue of the human disease. At present, it is unknown why loss of Phex function leads to cartilage abnormalities in Hyp mice. In the present study, we compared in wild-type and Hyp mice Phex protein localization in cartilage of developing long bone as well as localization of skeletal matrix proteins and matrix metalloproteinase-9 (MMP-9). Also compared were chondrocyte apoptosis in the growth plate, mineralization and cartilage remnant retention in the metaphysis, and chondroclast/osteoclast characteristics in the primary spongiosa. Phex protein was detected in proliferating and hypertrophic chondrocytes in growth plate cartilage of wild-type mice, but not in Hyp mice. Hyp mice exhibited a widened and irregular hypertrophic zone in growth plate cartilage showing hypomineralization, increased cartilage remnants from the growth plate in both metaphyseal trabecular and cortical bone, and fewer and smaller chondroclasts/osteoclasts in the primary spongiosa. Increased link protein and C-propeptide of type II procollagen of Hyp mice reflected the increase in chondrocytes and matrix in the cartilaginous growth plate and in bone. In addition, growth plate osteocalcin and bone sialoprotein levels were decreased, while osteonectin was increased, in hypertrophic chondrocytes and cartilage matrix in Hyp mice. MMP-9 in hypertrophic chondrocytes was also reduced in Hyp mice and fewer apoptotic hypertrophic chondrocytes were detected. These findings suggest that Phex may control mineralization and removal of hypertrophic chondrocytes and cartilage matrix in growth plate by regulating the synthesis and deposition of certain bone matrix proteins and proteases such as MMP-9. |
| Databáze: | OpenAIRE |
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