TY - JOUR
T1 - 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
AU - Muratovic, D.
AU - Findlay, D. M.
AU - Quarrington, R. D.
AU - Cao, X.
AU - Solomon, L. B.
AU - Atkins, G. J.
AU - Kuliwaba, J. S.
N1 - Funding Information:
The authors acknowledge funding from the National Health and Medical Research Council of Australia (NHMRC, Project Grant No. 1138865 ). DM is the recipient of an 2021 Arthritis Australia Fellowship.
Funding Information:
We also acknowledge travel funding provided by the International Synchrotron Access Program (ISAP) managed by the Australian Synchrotron, part of ANSTO, and funded by the Australian Government.
Publisher Copyright:
© 2022 Osteoarthritis Research Society International
PY - 2022/6
Y1 - 2022/6
N2 - Objective: 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. Design: 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). Results: 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]). Conclusion: 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.
AB - Objective: 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. Design: 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). Results: 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]). Conclusion: 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.
KW - Active TGFβ1
KW - Cartilage degeneration
KW - Human knee osteoarthritis
KW - Subchondral bone
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U2 - 10.1016/j.joca.2022.03.004
DO - 10.1016/j.joca.2022.03.004
M3 - Article
C2 - 35331858
AN - SCOPUS:85128221367
SN - 1063-4584
VL - 30
SP - 896
EP - 907
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
IS - 6
ER -