Characterisation of joint macrophages: implications for osteoarthritis

Garcia, J.; Wei, W.; Wright, K.; Mennan, C.; Roberts, S.; Richardson, J.; van Osch, G. J. V. M.; Bastiaansen-Jenniskens, Y.

Abstract

Introduction Inflammation in the synovium is a feature of osteoarthritis (OA) that contributes to the general degradation of the joint by the secretion of pro-inflammatory molecules and degradative enzymes. The infrapatellar fat pad (IPFP) is an intracapsular and extra-synovial adipose tissue that is also a source of pro-inflammatory molecules. Macrophages that reside in both the IPFP and synovium can exist in an M1 (pro-inflammatory) or M2 (ant-inflammatory) polarisation state. In this study, we have characterised the macrophage population in donor-matched IPFP and synovium, and assessed their modulation within the IPFP.

Materials and Methods Donor-matched IPFP and synovium tissues were obtained from patients with various arthropathies. Tissues were sectioned and immunohistochemistry was used to reveal the presence of cells that were positive for CD68 (pan macrophage marker), CD86 (M1), CD206 (M2) and arginase-1 (M2). IPFP explants were treated with the corticosteroid, triamcinolone, after which the tissues were digested to obtain the stromal fraction. Flow cytometry was used to assess the phenotype of the macrophages, using CD14 (pan macrophage marker), CD163 (M2) and CD86 (M1).

Results The IPFP and synovium were positive for both M1 and M2 macrophages markers. There was a strong correlation of CD68 positivity between the synovium and the stroma, but not between the synovium and IPFP or the stroma and IPFP. A similar trend was observed for CD206, but arginase-1 correlated positively between the synovium and FP. More CD14 + CD163 + cells were present in the stromal fraction of IPFP explants treated with triamcinolone (74.1%), compared to untreated controls (49.6%). CD14 + CD86 + cells were moderately increased after treatment (82.2%) compared to controls (77.7%). A co-positivity of CD163 and CD86 was observed regardless of treatment.

Discussion Our data suggests that there is no correlation between the presence of macrophages in the IPFP and synovium, which could indicate that these tissues function differentially with regard to macrophage prevalence and macrophage associated-inflammation. We have also demonstrated that the phenotype of macrophages can be modulated in situ towards an anti-inflammatory phenotype. These findings have significant implications in understanding the role of macrophages in the progression of OA and in developing therapies to target macrophage related joint inflammation.

Citation

Garcia, J., Wei, W., Wright, K., Mennan, C., Roberts, S., Richardson, J., …Bastiaansen-Jenniskens, Y. (2017). Characterisation of joint macrophages: implications for osteoarthritis. International Journal of Experimental Pathology, 97(6),

• Journal Article Type: Conference Paper
• Online Publication Date: Mar 29, 2017
• Publication Date: Mar 29, 2017
• Deposit Date: Jun 8, 2023
• Journal: International Journal of Experimental Pathology
• Print ISSN: 0959-9673
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 97
• Issue: 6
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/iep.12211