Increased Ratio of CD14++CD80+ Cells/CD14++CD163+ Cells in the Infrapatellar Fat Pad of End-Stage Arthropathy Patients.

Shuhe Ma,Kosaku Murakami,Tsuneyo Mimori,Shuji Akizuki,Hajime Yoshifuji,Masao Tanaka,Koji Kitagori,Hiromu Ito,Akio Morinobu,Rintaro Saito,Masahi Taniguchi,Koichi Murata,Kohei Nishitani,Koichiro Ohmura,Motomu Hashimoto,Ran Nakashima

doi:10.3389/fimmu.2021.774177

Abstract

ObjectivesThis study sought to identify the ratio of M1/M2 cells in the infrapatellar fat pads (IFP) and subcutaneous fat tissues (SC) of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. The clinical features of OA and RA patients treated with or without biological disease-modifying anti-rheumatic drugs (bDMARDs) were also assessed.MethodsIFP and SC were collected from patients with OA and RA who are undergoing total knee arthroplasty (TKA). CD14-positive cells were then isolated from these samples. Flow cytometry was used to determine the number of CD14++CD80+ cells and CD14++CD163+ cells. The expression levels of lipid transcription factors, such as sterol regulatory element-binding protein 1 (SREBP1) and liver X receptor alpha (LXRA), and inflammatory cytokines were also evaluated.ResultsTwenty OA patients and 22 RA patients were enrolled in this study. Ten of the RA patients (45.4%) received bDAMRDs before TKA. On average, a fivefold increase in the number of CD14-positive cells and lower expression levels of SREBP1C and LXRA were observed in OA IFP relative to OA SC; however, these results were not obtained from the RA samples. The median ratio of CD14++CD80+ cells/CD14++CD163+ cells of OA IFP was 0.87 (0.76–1.09, interquartile range), which is higher to that of OA SC with a lower ratio (p = 0.05835).ConclusionsThe quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients. To our knowledge, this is the first study to characterize the ratio of M1/M2 cells in the IFP and SC of end-stage OA and RA patients. The increased ratio of CD14++CD80+ cells/CD14++CD163+ cells in the IFP from patients with OA and RA treated with bDMARDs indicated that inflammation was localized in the IFP. As adipose tissue-derived innate immune cells were revealed as one of the targets for regulating inflammation, further analysis of these cells in the IFP may reveal new therapeutic strategies for inflammatory joint diseases.

Highlights

Osteoarthritis (OA) and rheumatoid arthritis (RA) affects millions of people worldwide, with one in three people over the age of 65 having OA [1], and every five out of a thousand people suffer from RA [2]
A fivefold increase in the number of CD14-positive cells and lower expression levels of SREBP1C and liver X receptor alpha (LXRA) were observed in OA infrapatellar fat pads (IFP) relative to OA subcutaneous fat tissues (SC); these results were not obtained from the RA samples
The quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients

Summary

Introduction

Osteoarthritis (OA) and rheumatoid arthritis (RA) affects millions of people worldwide, with one in three people over the age of 65 having OA [1], and every five out of a thousand people suffer from RA [2]. OA and RA are characterized by joint pain; in some cases, they are characterized by deformity owing to inadequate therapeutic strategies. The progression of OA can be seen as multiple reasons, such as mechanical stress to the cartilage [3, 4], subchondral bone remodeling [5], biochemical cascades [6], and inflammation [5, 6]. RA is an autoimmune disease that causes inflammation in the synovial tissue [3, 7]. Disease-modifying anti-rheumatic drugs (DMARDs), such as biological DMARDs (bDMARDs), are used to treat RA [8]; currently, no disease-modifying therapeutics is available for OA patients. Elderly patients with OA or RA sometimes opt for total knee arthroplasty (TKA) to restore joint function

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