Functional analysis of synovial fluid from osteoarthritic knee and carpometacarpal joints unravels different molecular profiles

Barreto, Gonçalo; Soliymani, Rabah; Baumann, Marc; Waris, Eero; Eklund, Kari K.; Zenobi‐Wong, Marcy; Łałowski, Maciej

doi:10.1093/rheumatology/key232

Cited by 10 publications

(7 citation statements)

References 41 publications

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“…SF samples of non-erosive OA from the carpometacarpal joints (CMC-I) and of primary idiopathic knee OA patients were investigated by quantitative liquid chromatography mass spectrometry (LC-MS), and revealed multiple peptide differences, including CLU, paraoxonase/arylesterase 1 (PON1) and transthyretin [ 72 ]. In the knee OA group, 28 proteins were up-regulated and 12 down-regulated, as compared to CMC-I group, while 16 of those up-regulated and 3 of down-regulated proteins were linked to inflammatory processes in the joint and lipid transport.…”

Section: Clu As a Translational Biomarker Of Oamentioning

confidence: 99%

“…Higher CLU concentrations (∼1.7-fold increase) were detected in SFs from knee OA patients than in ones from CMC-I OA. These differences in CLU levels might have occurred because the weight-bearing (knee OA) and non-weight bearing (CMC-I) joints were analysed and compared [ 72 ]. Changes in CLU levels in healthy vs .…”

Section: Clu As a Translational Biomarker Of Oamentioning

confidence: 99%

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Exploring the translational potential of clusterin as a biomarker of early osteoarthritis

Kalvaityte

Matta

Bernotienė

et al. 2022

Journal of Orthopaedic Translation

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Background Clusterin (CLU; also known as apolipoprotein J) is an ATP-independent holdase chaperone that prevents proteotoxicity as a consequence of protein aggregation. It is a ∼60 kDa disulfide-linked heterodimeric protein involved in the clearance of cellular debris and the regulation of apoptosis. CLU has been proposed to protect cells from cytolysis by complement components and has been implicated in Alzheimer’s disease due to its ability to bind amyloid-β peptides and prevent aggregate formation in the brain. Recent studies suggest that CLU performs moonlighting functions. CLU exists in two major forms: an intracellular form and a secreted extracellular form. The intracellular form of CLU may suppress stress-induced apoptosis by forming complexes with misfolded proteins and facilitates their degradation. The secreted form of CLU functions as an extracellular chaperone that prevents protein aggregation. Methods In this review, we discuss the published literature on the biology of CLU in cartilage, chondrocytes, and other synovial joint tissues. We also review clinical studies that have examined the potential for using this protein as a biomarker in synovial and systemic fluids of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Results Since CLU functions as an extracellular chaperone, we propose that it may be involved in cytoprotective functions in osteoarticular tissues. The secreted form of CLU can be measured in synovial and systemic fluids and may have translational potential as a biomarker of early repair responses in OA. Conclusion There is significant potential for investigating synovial and systemic CLU as biomarkers of OA. Future translational and clinical orthopaedic studies should carefully consider the diverse roles of this protein and its involvement in other comorbidities. Therefore, future biomarker studies should not correlate circulating CLU levels exclusively to the process of OA pathogenesis and progression. Special attention should be paid to CLU levels in synovial fluid. The Translational potential of this article There is significant potential for investigating synovial and systemic CLU as a predictive biomarker of osteoarthritis (OA) progression and response to novel treatments and interventions. Given that CLU plays diverse roles in other comorbidities such as rheumatoid arthritis (RA) and obesity, future translational and clinical orthopaedic biomarker studies should not directly correlate circulating CLU levels to the process of OA pathogenesis and progression. However, special attention should be paid to CLU levels in synovial fluid. The cytoprotective properties of CLU may support the implementation of regenerative strategies and new approaches for developing targeted therapeutics for OA.

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Section: Clu As a Translational Biomarker Of Oamentioning

confidence: 99%

Section: Clu As a Translational Biomarker Of Oamentioning

confidence: 99%

Exploring the translational potential of clusterin as a biomarker of early osteoarthritis

Kalvaityte

Matta

Bernotienė

et al. 2022

Journal of Orthopaedic Translation

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“…Previous studies showed that levels of IL-6 in SF can vary between different joints, which could direct future IL-6 targeted therapy towards relevant patient subgroups. For example, levels of IL-6 were strikingly higher in knee OA SF compared with carpometacarpal joint fluid [ 120 ]. Moreover, more IL-6 was detected in post-traumatic wrist OA compared with knee OA patients [ 121 ].…”

Section: Under Construction: Il-6 Targeted Therapy In Oamentioning

confidence: 99%

A roadmap to target interleukin-6 in osteoarthritis

2020

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Joint inflammation is present in the majority of OA patients and pro-inflammatory mediators, such as IL-6, are actively involved in disease progression. Increased levels of IL-6 in serum or synovial fluid from OA patients correlate with disease incidence and severity, with IL-6 playing a pivotal role in the development of cartilage pathology, e.g. via induction of matrix-degrading enzymes. However, IL-6 also increases expression of anti-catabolic factors, suggesting a protective role. Until now, this dual role of IL-6 is incompletely understood and may be caused by differential effects of IL-6 classic vs trans-signalling. Here, we review current evidence regarding the role of IL-6 classic- and trans-signalling in local joint pathology of cartilage, synovium and bone. Furthermore, we discuss targeting of IL-6 in experimental OA models and provide future perspective for OA treatment by evaluating currently available IL-6 targeting strategies.

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“…SF ensures joint lubrication and delivery of nutrients and other essential molecules to articular cartilage 5,6 . A disturbance in SF composition might adversely affect joint homeostasis and result in OA initiation or worsening 3,4,7,8 . In general, OA synovial fluid (OASF) contains increased levels of cytokines, chemokines and damage-associated molecular patterns (DAMPs) 2 .…”

Section: Introductionmentioning

confidence: 99%

“…In line with this, an increased synovial fluid level of vascular endothelial growth factor (VEGF) in OA patients is known to induce vascular hyperpermeability 11 . While the compositional change of SF is evident in OA 12 , only a limited number of studies investigated the direct effects of OASF on chondrocytes 8,13 . Our recent work unraveled the first key underlying mechanisms by which OASF induced chondrocyte dedifferentiation, fibrosis and proliferation 14 .…”

Section: Introductionmentioning

confidence: 99%

Direct comparison of non-osteoarthritic and osteoarthritic synovial fluid-induced intracellular chondrocyte signaling and phenotype changes

Housmans

Akker²,

Neefjes³

et al. 2023

Osteoarthritis and Cartilage

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Functional analysis of synovial fluid from osteoarthritic knee and carpometacarpal joints unravels different molecular profiles

Cited by 10 publications

References 41 publications

Exploring the translational potential of clusterin as a biomarker of early osteoarthritis

Exploring the translational potential of clusterin as a biomarker of early osteoarthritis

A roadmap to target interleukin-6 in osteoarthritis

Direct comparison of non-osteoarthritic and osteoarthritic synovial fluid-induced intracellular chondrocyte signaling and phenotype changes

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