Characterization of normal murine carpal bone development prompts re-evaluation of pathological osteolysis as the cause of human carpal-tarsal osteolysis disorders

Lazarus, Syndia, Tseng, Hsu-Wen, Lawrence, Felicity, Woodruff, Maria Ann, Duncan, Emma Letitia and Pettit, Allison Robyn (2017) Characterization of normal murine carpal bone development prompts re-evaluation of pathological osteolysis as the cause of human carpal-tarsal osteolysis disorders. American Journal of Pathology, 187 9: 1923-1934. doi:10.1016/j.ajpath.2017.05.007


Author Lazarus, Syndia
Tseng, Hsu-Wen
Lawrence, Felicity
Woodruff, Maria Ann
Duncan, Emma Letitia
Pettit, Allison Robyn
Title Characterization of normal murine carpal bone development prompts re-evaluation of pathological osteolysis as the cause of human carpal-tarsal osteolysis disorders
Journal name American Journal of Pathology   Check publisher's open access policy
ISSN 0002-9440
1525-2191
Publication date 2017-09-01
Year available 2017
Sub-type Article (original research)
DOI 10.1016/j.ajpath.2017.05.007
Open Access Status Not yet assessed
Volume 187
Issue 9
Start page 1923
End page 1934
Total pages 12
Place of publication New York, NY, United States
Publisher Elsevier
Language eng
Abstract 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.
Keyword Bone formation
Multicentric carpotarsal osteolysis
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID GNT1056015
Institutional Status UQ

 
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Created: Fri, 15 Sep 2017, 10:23:01 EST by Dr Allison Pettit on behalf of Mater Research Institute-UQ