The Potential of Multiple Synovial-Fluid Protein-Concentration Analyses in the Assessment of Knee Osteoarthritis

Driban, Jeffrey B.; Balasubramanian, Easwaran; Amin, Mamta; Sitler, Michael R.; Ziskin, Marvin C.; Barbe, Mary F.

doi:10.1123/jsr.19.4.411

Cited by 13 publications

(11 citation statements)

References 45 publications

(47 reference statements)

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“…Within the present study, no significant differences in TIMP expression (1, 2, 3, or 4) were detected between normal and early OA synovial fluid, which is consistent with the findings that normal and early OA synovial fluid could not be segregated based on MMP expression levels alone. Overall the published data seems to suggest that TIMP levels do not increase significantly with the severity of OA [34,35], however, TIMP 1 levels decrease within injured joints [36]. Based on results present here and previous studies it would appear that the regulation of MMPs by TIMPs may be important in the progression of disease, however, it also appears that it cannot be clearly understood solely through the quantification and/or ratio of MMPs to TIMPs.…”

Section: Discussionmentioning

confidence: 45%

Matrix metalloproteinase protein expression profiles cannot distinguish between normal and early osteoarthritic synovial fluid

Heard

Martin

Rattner

et al. 2012

BMC Musculoskelet Disord

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BackgroundOsteoarthritis (OA) and Rheumatoid arthritis (RA) are diseases which result in the degeneration of the joint surface articular cartilage. Matrix Metalloproteinases (MMPs) are enzymes that aid in the natural remodelling of tissues throughout the body including cartilage. However, some MMPs have been implicated in the progression of OA and RA as their expression levels and activation states can change dramatically with the onset of disease. Yet, it remains unknown if normal and arthritic joints demonstrate unique MMPs expression profiles, and if so, can the MMP expression profile be used to identify patients with early OA. In this study, the synovial fluid protein expression levels for MMPs 1, 2, 3, 7, 8, 9, 12 & 13, as well as those for the Tissue Inhibitors of MMPs (TIMPs) 1, 2, 3, & 4 were examined in highly characterized normal knee joints, and knee joints with clinically diagnosed OA (early and advanced) or RA. The purpose of this study was to determine if normal, OA, and RA patients exhibit unique expression profiles for a sub-set of MMPs, and if early OA patients have a unique MMP expression profile that could be used as an early diagnostic marker.MethodsSynovial fluid was aspirated from stringently characterized normal knee joints, and in joints diagnosed with either OA (early and advanced) or RA. Multiplexing technology was employed to quantify protein expression levels for 8 MMPs and 4 TIMPs in the synovial fluid of 12 patients with early OA, 17 patients diagnosed with advanced OA, 15 with RA and 25 normal knee joints. Principle component analysis (PCA) was used to reveal which MMPs were most influential in the distinction between treatment groups. K – means clustering was used to verify the visual grouping of subjects via PCA.ResultsSignificant differences in the expression levels of MMPs and TIMPs were observed between normal and arthritic synovial fluids (with the exception of MMP 12). PCA demonstrated that MMPs 2, 8 & 9 can be used to effectively separate individuals diagnosed with advanced arthritis from early osteoarthritic and normal individuals, however, these MMP profiles do not separate early OA from normal synovial fluid. An apparent separation between advanced OA and RA subjects was also revealed through PCA. K-means clustering verified the presence of 3 clusters: normal joints clustered with early OA, and separate clusters of advanced OA or RA.ConclusionsThis study demonstrates that unique MMP and TIMP expression profiles are present within normal, advanced OA and RA synovial fluid. These MMP profiles can be used to distinguish advanced OA & RA synovial fluid from early OA & normal synovial fluid, and even between synovial fluid samples from OA and RA joints. Although this methodology cannot be used for the diagnosis of early OA, high throughput multiplex technology of MMPs and TIMPs in synovial fluid may prove useful in determining the severity of the disease state, and/or quantifying the response of individuals to disease interventions.

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Section: Discussionmentioning

confidence: 45%

Matrix metalloproteinase protein expression profiles cannot distinguish between normal and early osteoarthritic synovial fluid

Heard

Martin

Rattner

et al. 2012

BMC Musculoskelet Disord

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“…It could be surmised that biological markers would be more suitable for identification of the profile of generalized osteoarthritis, while imaging markers would be more effective for exploration of local effects post-trauma. Similarly, within the range of biomarkers, serum measurements may provide a better measure of generalized osteoarthritis (cartilage and bone sources), while intra-articular biomarkers may better characterize local osteoarthritis [ 41 , 42 ]. Ongoing genetic studies in more than 2,500 patients with generalized osteoarthritis are set to detect linkage of circulating biomarkers to osteoarthritis-associated genes, and may shed further light on the possibilities of genetic profiling for the disease [ 43 ].…”

Section: Process and Outcomesmentioning

confidence: 99%

Can We Identify Patients with High Risk of Osteoarthritis Progression Who Will Respond to Treatment? A Focus on Epidemiology and Phenotype of Osteoarthritis

et al. 2015

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Osteoarthritis is a syndrome affecting a variety of patient profiles. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the European Union Geriatric Medicine Society working meeting explored the possibility of identifying different patient profiles in osteoarthritis. The risk factors for the development of osteoarthritis include systemic factors (e.g., age, sex, obesity, genetics, race, and bone density) and local biomechanical factors (e.g., obesity, sport, joint injury, and muscle weakness); most also predict disease progression, particularly joint injury, malalignment, and synovitis/effusion. The characterization of patient profiles should help to better orientate research, facilitate trial design, and define which patients are the most likely to benefit from treatment. There are a number of profile candidates. Generalized, polyarticular osteoarthritis and local, monoarticular osteoarthritis appear to be two different profiles; the former is a feature of osteoarthritis co-morbid with inflammation or the metabolic syndrome, while the latter is more typical of post-trauma osteoarthritis, especially in cases with severe malalignment. Other biomechanical factors may also define profiles, such as joint malalignment, loss of meniscal function, and ligament injury. Early- and late-stage osteoarthritis appear as separate profiles, notably in terms of treatment response. Finally, there is evidence that there are two separate profiles related to lesions in the subchondral bone, which may determine benefit from bone-active treatments. Decisions on appropriate therapy should be made considering clinical presentation, underlying pathophysiology, and stage of disease. Identification of patient profiles may lead to more personalized healthcare, with more targeted treatment for osteoarthritis.

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“…There is evidence of a biosynthetic attempt to control proinflammatory and catabolic events as evidenced by increased tissue inhibitor of MMPs (TIMP)-1, TIMP-2 and IL-10 in synovial fluid of patients with OA ( Figure 2) 20,21 . Despite an attempt to re-establish homeostasis, the catabolic pathways lead to increased extracellular matrix permeability and increased water content in articular cartilage 22 , thus pathologically altering the biochemical and biomechanical properties of the articular cartilage.…”

Section: Biochemical-biomechanical Interactionmentioning

confidence: 99%

Joint trauma initiates knee osteoarthritis through biochemical and biomechanical processes and interactions

Cattano¹,

Barbe²,

Massicotte³

et al. 2013

OA Musculoskeletal Medicine

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IntroductionGlobally, knee osteoarthritis (OA) is among the top 15 causes of disability. A patient with a history of macrotrauma is more than four times as likely to develop knee OA. Macrotrauma initiates a cascade of biochemical and biomechanical changes in the joint that interact and can lead to joint failure. The purpose of this critical review is to present an overview of the early pathophysiological (i.e. biomechanical and biochemical) changes that typically occur after a knee injury and the implications of these changes for early-stage OA interventions.

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The Potential of Multiple Synovial-Fluid Protein-Concentration Analyses in the Assessment of Knee Osteoarthritis

Cited by 13 publications

References 45 publications

Matrix metalloproteinase protein expression profiles cannot distinguish between normal and early osteoarthritic synovial fluid

Matrix metalloproteinase protein expression profiles cannot distinguish between normal and early osteoarthritic synovial fluid

Can We Identify Patients with High Risk of Osteoarthritis Progression Who Will Respond to Treatment? A Focus on Epidemiology and Phenotype of Osteoarthritis

Joint trauma initiates knee osteoarthritis through biochemical and biomechanical processes and interactions

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