Dear Editor,
Currently, no biomarkers are available for structural changes in osteoarthritis structural disease in osteoarthritis (OA) (1). Increase in the permeability of the synovial/blood barrier in OA enables greater exchange between the synovial cavity and systemic circulation. Thus, it is possible to identify systemic biomarkers relevant to prognosis, diagnosis, or phenotyping that may reflect changes in the synovial cavity. We aimed to correlate the levels of potential biomarkers associated with OA in synovial fluid and serum of patients with knee OA to understand whether local changes in these mediators are reflected systemically. We focused on senescence-associated secretory factors because advanced age is a major risk factor and senescence is implicated in aging and OA. To our knowledge, no previous studies have assessed this correlation. We recruited community-dwelling, ambulatory patients with knee OA from rheumatology clinic at Boston Medical Center, Boston, MA, USA. All participants underwent knee effusion aspiration at least once on a prior visit to exclude inflammatory and crystal arthritis. The knee synovial fluid that was aspirated for usual care during clinic visit and blood were collected contemporaneously and stored at −80°C. The synovial fluid and serum were analyzed by multiplex enzyme-linked immunosorbent assay (ELISA ) using a Luminex analyzer for metalloproteinases, growth factors, and related anabolic proteins, cytokines, chemokines, proteases, adhesion molecules, and collagen proteins. Pearson’s correlation was used to assess correlations between markers in synovial fluid and serum using SAS 9.3. We included eight participants (mean age, 70.8±15.6 years; 87.5% women; and mean BMI, 34.1±8.9 kg/m2). The results did not reach statistical significance due to small numbers; however, based on the correlation co-efficient, we found some factors that were strongly correlated (Table 1) in synovial fluid and serum. This first exploratory project provides insight into how strongly some systemic markers may be reflective of OA-related processes arising from joint pathology. Further largescale studies are required to validate our findings and examine the association between systemic biomarkers and structural and symptomatic outcomes in OA.
Table 1.
Correlation between senescence-associated secretory factors in synovial fluid and serum and osteoarthritis.
| Analyte | Category | SF pg/mL Median (IQR) |
Serum pg/mL Median (IQR) |
Rho | p |
|---|---|---|---|---|---|
| STRONGLY CORRELATED (Rho≥0.5) | |||||
|
| |||||
| CXCL13 | Chemokine | 103.6 (15.2) | 92.8 (62.5) | 0.7479 | 0.03 |
| uPAR | Proteinases | 2322.5 (1894) | 1067.9 (798.7) | 0.6474 | 0.08 |
| MMP12 | Proteinases | 147.3 (24.9) | 159.7 (17.1) | 0.6350 | 0.09 |
| ICAM-1 | Adhesion molecule | 161834.5 (165368) | 157307.5 (230114) | 0.6290 | 0.09 |
| CCL11 | Chemokine | 177.9 (62.9) | 236.3 (44.8) | 0.6116 | 0.11 |
| IL-1b | Interleukin | 20.2 (1.04) | 24.6 (2.86) | 0.5795 | 0.13 |
| CXCL1 | Chemokine | 507.6 (199.54) | 446.4 (253.49) | 0.5671 | 0.14 |
| IGFBP7 | Growth factor | 17024.5 (5899) | 28820.5 (15871) | 0.5609 | 0.15 |
| PAI-1 | Protease inhibitor | 14487.0 (5467) | 14487.0 (0) | 0.5574 | 0.15 |
| CCL1 | Chemokine | 8.5 (2.28) | 8.7 (1.12) | 0.5335 | 0.17 |
| IGFBP3 | Growth factor | 263111 (276567) | 827635 (773075) | 0.5272 | 0.18 |
| MMIF | Chemokine | 11578.5 (4044) | 1637.5 (599.00) | 0.5113 | 0.20 |
IQR: interquartile range; uPAR: urokinase receptor; ICAM: intercellular adhesion mollecule-1; IGFBP: Insulin growth factor binding protein; MMIF: Macrophage migration inhibitory factor; PAI: plasminogen activator inhibitor.
Footnotes
Peer-review: Externally peer-reviewed.
Author Contributions: Concept - D.M., C.S., D.F.; Design - J.E.R., D.M., C.S., D.T.F.; Supervision - D.M., C.S., D.T.F.; Resources - D.M., D.T.F.; Materials - D.M., D.T.F.; Data Collection and/or Processing - M.B.A., J.G., A.P., D.M.; Analysis and/or Interpretation - J.E.R., C.S., D.T.F., M.B.A., D.M.; Literature Search - J.E.R., D.M.; Writing Manuscript - J.E.R., D.M.; Critical Review - J.E.R., C.S., D.T.F., M.B.A., J.G., A.P., D.M.
Conflict of Interest: The authors have no conflict of interest to declare.
Financial Disclosure: The authors declared that this study has received no financial support.
Reference
- 1.Hunter DJ, Nevitt M, Losina E, Kraus V. Biomarkers for osteoarthritis: Current position and steps towards further validation. Best Pract Res Clin Rheumatol. 2014;28:61–71. doi: 10.1016/j.berh.2014.01.007. [DOI] [PMC free article] [PubMed] [Google Scholar]