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Loading-Induced Reduction in Sclerostin as a Mechanism of Subchondral Bone PlateSclerosis in Mouse Knee Joints During Late-Stage Osteoarthritis
Journal article   Open access

Loading-Induced Reduction in Sclerostin as a Mechanism of Subchondral Bone PlateSclerosis in Mouse Knee Joints During Late-Stage Osteoarthritis

Haoruo Jia, Xiaoyuan Ma, Yulong Wei, Wei Tong, Robert J. Tower, Abhishek Chandra, Luqiang Wang, Zeyang Sun, Zhaochun Yang, Farid Badar, …
Arthritis & rheumatology (Hoboken, N.J.), v 70(2)
01 Feb 2018
DOI: https://doi.org/10.1002/art.40351
PMID: 29024567
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc5788711View
Accepted (AM) Open Open Access (License Unspecified)

Abstract

Life Sciences & Biomedicine Rheumatology Science & Technology
Objective. To establish an unbiased, 3-dimensional (3-D) approach that quantifies subchondral bone plate (SBP) changes in mouse joints, and to investigate the mechanism that mediates SBP sclerosis at a late stage of osteoarthritis (OA). Methods. A new micro-computed tomography (micro-CT) protocol was developed to characterize the entire thickness of the SBP in the distal femur of a normal mouse knee. Four mouse models of severe joint OA were generated: cartilage-specific Egfr-knockout (Egfr-CKO) mice at 2 months after surgical destabilization of the medial meniscus (DMM), Egfr-CKO mice with aging-related spontaneous OA, wild-type (WT) mice at 10 months after DMM, and WT mice at 14 weeks after DMM plus hemisectomy of the meniscus (DMMH) surgery. As an additional model, mice with knockout of the sclerostin gene (Sost-KO) were subjected to DMMH surgery. Knee joints were examined by micro-CT, histology, and immunohistochemical analyses. Results. Examination of the mouse distal femur by 3-D micro-CT revealed a positive correlation between SBP thickness and the loading status in normal knees. In all 4 mouse models of late-stage OA, SBP sclerosis was restricted to the areas under severely eroded articular cartilage. This was accompanied by elevated bone formation at the bone marrow side of the SBP and a drastic reduction in the levels of sclerostin in osteocytes within the SBP. Unlike in WT mice, no further increase in the thickness of the SBP was observed in response to DMMH in Sost-KO mice. Conclusion. Since focal stress on the SBP underlying sites of cartilage damage increases during late stages of OA, these findings establish mechanical loading-induced attenuation of sclerostin expression and elevation of bone formation along the SBP surface as the major mechanisms characterizing subchondral bone phenotypes associated with severe late-stage OA in mice.

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61 citations in Web of Science
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Collaboration types
Industry collaboration
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International collaboration
Web of Science research areas
Rheumatology
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