Author:
Tenshin Hirofumi,Delgado-Calle Jesus,Windle Jolene J.,Roodman G. David,Chirgwin John M.,Kurihara Noriyoshi
Abstract
Abstract
Purpose of Review
To describe the contributions of osteocytes to the lesions in Paget’s disease, which are characterized by locally overactive bone resorption and formation.
Recent Findings
Osteocytes, the most abundant cells in bone, are altered in Paget’s disease lesions, displaying increased size, decreased canalicular length, incomplete differentiation, and less sclerostin expression compared to controls in both patients and mouse models. Pagetic lesions show increased senescent osteocytes that express RANK ligand, which drives osteoclastic bone resorption. Abnormal osteoclasts in Paget’s disease secrete abundant IGF1, which enhances osteocyte senescence, contributing to lesion formation.
Summary
Recent data suggest that osteocytes contribute to lesion formation in Paget’s disease by responding to high local IGF1 released from abnormal osteoclasts. Here we describe the characteristics of osteocytes in Paget’s disease and their role in bone lesion formation based on recent results with mouse models and supported by patient data.
Funder
National Institute of Arthritis and Musculoskeletal and Skin Diseases
NIH-NCI Cancer Center Support grant
Publisher
Springer Science and Business Media LLC
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