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https://hdl.handle.net/2440/135118
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Type: | Journal article |
Title: | Elevated levels of active Transforming Growth Factor β1 in the subchondral bone relate spatially to cartilage loss and impaired bone quality in human knee osteoarthritis |
Other Titles: | Elevated levels of active Transforming Growth Factor beta1 in the subchondral bone relate spatially to cartilage loss and impaired bone quality in human knee osteoarthritis |
Author: | Muratovic, D. Findlay, D.M. Quarrington, R.D. Cao, X. Solomon, L.B. Atkins, G.J. Kuliwaba, J.S. |
Citation: | Osteoarthritis and Cartilage, 2022; 30(6):896-907 |
Publisher: | Elsevier BV |
Issue Date: | 2022 |
ISSN: | 1063-4584 1522-9653 |
Statement of Responsibility: | D. Muratovic, D.M. Findlay, R.D. Quarrington, X. Cao, L.B. Solomon, G.J. Atkins, J.S. Kuliwaba |
Abstract: | <h4>Objective</h4>The association between the spatially distributed level of active TGFβ1 in human subchondral bone, and the characteristic structural and cellular parameters of human knee OA, was assessed.<h4>Design</h4>Paired subchondral bone samples from 35 OA arthroplasty patients, (15 men and 20 women, aged 69 ± 9 years) were obtained from beneath macroscopically present (CA+) or denuded cartilage (CA-) to determine the concentration of active TGFβ1 (ELISA) and its relationship to bone quality (synchrotron micro-CT), cellularity, and vascularization (histology).<h4>Results</h4>Bone samples beneath (CA-) regions had significantly increased concentrations of active TGFβ1 protein (mean difference: 26.4; 95% CI: [3.2, 49.7]), when compared to bone in CA + regions. Trabecular Bone below (CA-) regions had increased bone volume (median difference: 4.3; 96.49% CI: [-1.7, 17.8]), increased trabecular number (1.5 [0.006, 2.6], decreased trabecular separation (-0.05 [-0.1,-0.005]), and increased bone mineral density (394.5 [65.7, 723.3]) comparing to (CA+) regions. Further, (CA-) bone regions showed increased osteocyte density (0.012 [0.006, 0.018]), with larger osteocyte lacunae (39.8 [7.8, 71.7]) that were less spherical (-0.02 [-0.04, -0.003]), and increased bone matrix vascularity (12.4 [0.3, 24.5]) compared to (CA+). In addition, increased levels of active TGFβ1 related to increased bone volume (0.04 [-0.11, 0.9]), while increased OARSI grade associated with lacunar volume (-44.1 [-71.1, -17.2]), and orientation (2.7 [0.8, 4.6]).<h4>Conclusion</h4>Increased concentration of active TGFβ1 in the subchondral bone of human knee OA associates spatially with impaired bone quality and disease severity, suggesting that TGFβ1 is a potential therapeutic target to prevent or reduce human OA disease progression. |
Keywords: | Human knee osteoarthritis Subchondral bone Active TGβ1 Cartilage degeneration |
Rights: | © 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. |
DOI: | 10.1016/j.joca.2022.03.004 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1138865 |
Published version: | http://dx.doi.org/10.1016/j.joca.2022.03.004 |
Appears in Collections: | Orthopaedics and Trauma publications |
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