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

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dc.contributor.authorMuratovic, D.
dc.contributor.authorFindlay, D.M.
dc.contributor.authorQuarrington, R.D.
dc.contributor.authorCao, X.
dc.contributor.authorSolomon, L.B.
dc.contributor.authorAtkins, G.J.
dc.contributor.authorKuliwaba, J.S.
dc.date.issued2022
dc.description.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.
dc.description.statementofresponsibilityD. Muratovic, D.M. Findlay, R.D. Quarrington, X. Cao, L.B. Solomon, G.J. Atkins, J.S. Kuliwaba
dc.identifier.citationOsteoarthritis and Cartilage, 2022; 30(6):896-907
dc.identifier.doi10.1016/j.joca.2022.03.004
dc.identifier.issn1063-4584
dc.identifier.issn1522-9653
dc.identifier.orcidMuratovic, D. [0000-0002-3009-7881]
dc.identifier.orcidQuarrington, R.D. [0000-0002-0633-2482]
dc.identifier.orcidSolomon, L.B. [0000-0001-6254-2372]
dc.identifier.orcidAtkins, G.J. [0000-0002-3123-9861]
dc.identifier.orcidKuliwaba, J.S. [0000-0003-1942-9299]
dc.identifier.urihttps://hdl.handle.net/2440/135118
dc.language.isoen
dc.publisherElsevier BV
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1138865
dc.rights© 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.joca.2022.03.004
dc.subjectHuman knee osteoarthritis
dc.subjectSubchondral bone
dc.subjectActive TGβ1
dc.subjectCartilage degeneration
dc.titleElevated levels of active Transforming Growth Factor β1 in the subchondral bone relate spatially to cartilage loss and impaired bone quality in human knee osteoarthritis
dc.title.alternativeElevated levels of active Transforming Growth Factor beta1 in the subchondral bone relate spatially to cartilage loss and impaired bone quality in human knee osteoarthritis
dc.typeJournal article
pubs.publication-statusPublished

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