Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Feb 5;19(1):39.
doi: 10.1186/s12891-018-1955-4.

Serum and synovial fluid cytokine profiling in hip osteoarthritis: distinct from knee osteoarthritis and correlated with pain

Guomin Ren  1 , Ian Lutz  2 , Pamela Railton  3 , J Preston Wiley  1   4 , Jenelle McAllister  4 , James Powell  1   2 , Roman J Krawetz  5   6   7
Affiliations

Serum and synovial fluid cytokine profiling in hip osteoarthritis: distinct from knee osteoarthritis and correlated with pain

Guomin Ren et al. BMC Musculoskelet Disord. .

Abstract

Background: Inflammation is associated with the onset and progression of osteoarthritis in multiple joints. It is well known that mechanical properties differ between different joints, however, it remains unknown if the inflammatory process is similar/distinct in patients with hip vs. knee OA. Without complete understanding of the role of any specific cytokine in the inflammatory process, understanding the 'profile' of inflammation in a given patient population is an essential starting point. The aim of this study was to identify serum cytokine profiles in hip Osteoarthritis (OA), and investigate the association between cytokine concentrations and clinical measurements within this patient population and compare these findings to knee OA and healthy control cohorts.

Methods: In total, 250 serum samples (100 knee OA, 50 hip OA and 100 control) and 37 synovial fluid samples (8 knee OA, 14 hip OA and 15 control) were analyzed using a multiplex ELISA based approach. Synovial biopsies were also obtained and examined for specific cytokines. Pain, physical function and activity within the hip OA cohort were examined using the HOOS, SF-36, HHS and UCLA outcome measures.

Results: The three cohorts showed distinct serum cytokine profiles. EGF, FGF2, MCP3, MIP1α, and IL8 were differentially expressed between hip and knee OA cohorts; while FGF2, GRO, IL8, MCP1, and VEGF were differentially expressed between hip OA and control cohorts. Eotaxin, GRO, MCP1, MIP1β, VEGF were differentially expressed between knee OA and control cohorts. EGF, IL8, MCP1, MIP1β were differentially expressed in synovial fluid from a sub-set of patients from each cohort. Specifically within the hip OA cohort, IL-6, MDC and IP10 were associated with pain and were also found to be present in synovial fluid and synovial membrane (except IL-6) of patients with hip OA.

Conclusion: OA may include different inflammatory subtypes according to affected joints and distinct inflammatory processes may drive OA in these joints. IL6, MDC and IP10 are associated with hip OA pain and these proteins may be able to provide additional information regarding pain in hip OA patients.

Keywords: Hip; Inflammation; Osteoarthritis; Pain.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

This study protocol was approved by the University of Calgary Human Research Ethics Board (REB15–0880). Participants provided written consent. All research was performed in accordance with the Declaration of Helsinki

Consent for publication

All patient information has been de-identified.

Competing interests

Roman Krawetz is a member of the editorial board of BMC Musculoskeletal Disorders. The authors have no further conflicts of interest to disclose regarding the present study.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Comparison of cytokine profiles in serum in control, hip OA and knee OA cohorts. The serum concentrations of cytokines that were found to be significantly differently between the cohorts examined (a). The significantly different cytokines in each cohort are present in more detail in (b) after Bonferroni correction (p < 0.0012) (* = Significantly different in both serum and synovial fluid). Scatter plot of first 3 components of PCA of cytokine profiles of 3 cohorts demonstrates that the serum cytokine profiles are capable of discriminating the 3 different cohorts (c)
Fig. 2
Fig. 2
Differently expressed cytokines in synovial fluid in control, hip OA and knee OA cohorts. Of the cytokines examined in the serum that were significantly different between the hip OA, knee and control cohorts; EGF, MCP1, MIP1β and IL8 protein levels were also found to be significantly different between the synovial fluid samples obtained from the cohorts. Bonferroni correction (*p < 0.001)
Fig. 3
Fig. 3
Scatter plot of two cytokines and correlated pain scores. Left: IP10 (log transferred) was positively correlated with HOOS pain score (correlation = 0.294, p-value = 0.038). Middle: IP10 (log transferred) was positively correlated with HOOS pain question 8 (correlation = 0.390, p-value = 0.005). Right: MDC (log transferred) was negatively correlated with SF36 body pain score (correlation = − 0.302, p-value = 0.033)
Fig. 4
Fig. 4
Presence of MDC, IL6 and IP10 in Hip OA, Knee OA and control synovium, synovial fluid and serum. Representative images demonstrating the presence of MDC (orange) positive (MDC: 3/5 hip OA, 0/5 knee OA, 0/5 control) and IP10 (purple) positive (3/5 hip OA, 0/5 knee OA, 0/5 control) cells in synovium of Hip OA patients. IL-6 (green) positive cells within the synovium were not observed in the Hip OA cohort, but observed with the knee OA cohort (1/5 hip OA, 4/5 knee OA, 0/5 control) (a). Serum and synovial fluid levels of MDC, IL6 and IP10 were also examined in the three cohorts (b). Bonferroni correction (*p < 0.001)
See this image and copyright information in PMC

References

    1. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008;58(1):26–35. doi: 10.1002/art.23176. - DOI - PMC - PubMed
    1. Wright EA, Katz JN, Cisternas MG, Kessler CL, Wagenseller A, Losina E. Impact of knee osteoarthritis on health care resource utilization in a US population-based national sample. Med Care. 2010;48(9):785–791. doi: 10.1097/MLR.0b013e3181e419b1. - DOI - PMC - PubMed
    1. Ganz R, Leunig M, Leunig-Ganz K, Harris WH. The etiology of osteoarthritis of the hip: an integrated mechanical concept. Clin Orthop Relat Res. 2008;466(2):264–272. doi: 10.1007/s11999-007-0060-z. - DOI - PMC - PubMed
    1. Sandell LJ. Etiology of osteoarthritis: genetics and synovial joint development. Nat Rev Rheumatol. 2012;8(2):77–89. doi: 10.1038/nrrheum.2011.199. - DOI - PubMed
    1. Heard BJ, Rosvold JM, Fritzler MJ, El-Gabalawy H, Wiley JP, Krawetz RJ. A computational method to differentiate normal individuals, osteoarthritis and rheumatoid arthritis patients using serum biomarkers. J R Soc Interface. 2014;11(97):20140428. doi: 10.1098/rsif.2014.0428. - DOI - PMC - PubMed

Publication types

MeSH terms