Characterization of Normal Murine Carpal Bone Development Prompts Re-Evaluation of Pathologic Osteolysis as the Cause of Human Carpal-Tarsal Osteolysis Disorders
| Autor: | Syndia Lazarus, Maria A. Woodruff, Emma L. Duncan, Hsu-Wen Tseng, Allison R. Pettit, Felicity A. Lawrence |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty animal structures Osteolysis MafB Transcription Factor 030105 genetics & heredity Bone resorption Pathology and Forensic Medicine 03 medical and health sciences Mice Osteogenesis medicine Matrix Metalloproteinase 14 Animals Humans Growth Plate Intramolecular Lyases Endochondral ossification Carpal Bones Ossification business.industry Arabidopsis Proteins Cartilage Anatomy X-Ray Microtomography medicine.disease Enthesis body regions 030104 developmental biology medicine.anatomical_structure MAFB Child Preschool Matrix Metalloproteinase 2 medicine.symptom business Calcification |
| Zdroj: | The American journal of pathology. 187(9) |
| ISSN: | 1525-2191 |
| Popis: | Multicentric carpal-tarsal osteolysis; multicentric osteolysis, nodulosis, and arthropathy; and Winchester syndromes, skeletal dysplasias characterized by carpal/tarsal and epiphyseal abnormalities, are caused by mutations in v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B (MAFB), matrix metalloproteinase (MMP) 2, and MMP14, respectively; however, the underlying pathophysiology is unclear. Osteoclast-mediated osteolysis has been regarded as the main mechanism, but does not explain the skeletal distribution. We hypothesized that MAFB, MMP-2, and MMP-14 have integral roles in carpal/tarsal and epiphyseal bone development. Normal neonatal mouse forepaws were imaged by micro-computed tomography and examined histologically. Murine forepaw ossification occurred sequentially. Subarticular regions of endochondral ossification showed morphologic and calcification patterns that were distinct from archetypical physeal endochondral ossification. This suggests that two different forms of endochondral ossification occur. The skeletal sites showing the greatest abnormality in the carpal-tarsal osteolysis syndromes are regions of subarticular ossification. Thus, abnormal bone formation in areas of subarticular ossification may explain the site-specific distribution of the carpal-tarsal osteolysis phenotype. MafB, Mmp-2, and Mmp-14 were expressed widely, and tartrate-resistant acid phosphatase staining notably was absent in the subarticular regions of the cartilage anlagen and entheses at a time point most relevant to the human osteolysis syndromes. Thus, abnormal peri-articular skeletal development and modeling, rather than excessive bone resorption, may be the underlying pathophysiology of these skeletal syndromes. |
| Databáze: | OpenAIRE |
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