Abstract

Osteoarthritis (OA) is a degenerative disorder characterized by chondrocyte apoptosis and degeneration of articular cartilage resulting in loss of mobility and pain. Inflammation plays a key role in the development and progression of OA both on the side of apoptosis and repair, while its exact role in pathogenesis has yet to be fully elucidated. Few studies have examined the cellular composition (inflammatory cells and/or progenitor cells) in the synovium of patients with pre-OA (asymptomatic with cartilage damage). Therefore, in the current study, mesenchymal progenitor cells (MPCs) and macrophages were enumerated within normal, pre-OA and OA synovium. No differences were observed between MPCs in normal vs. pre-OA, however, fewer macrophages were observed in pre-OA vs. normal synovium. Osteoarthritic synovium contained greater numbers of both MPCs and macrophages. Interestingly, the localization of MPCs and macrophages was affected by disease severity. In normal and pre-OA synovium, MPCs and macrophages co-localized, while in OA synovium, MPCs and macrophage populations were spatially distinct. Examining the cellular interactions between MPCs and macrophages in synovium may be essential for understanding the role of these cells in the onset and/or pathogenesis of the disease. This study has provided a first step by examining these cell types both spatially and temporally (e.g., disease severity). Further cellular and molecular studies will be needed to determine the functions of these cells in the context of disease and in relation to each other and the joint as a whole.

Highlights

  • Osteoarthritis (OA) is a degenerative joint disorder that affects all tissues in synovial joints [1,2,3]

  • When comparing biopsies collected from the normal joint cohort at the intimal and subintimal tissue layers, no differences were observed in putative mesenchymal progenitor cells (MPCs) (CD90 or CD271 positive cells) (Figure 1K), while decreases in putative macrophages (CD14 or CD68 positive cells) were observed in the intimal layer compared to the subintimal layer (Figure 1K)

  • We identified that synovial macrophages are decreased in pre-OA joints vs. normal joints and that both MPCs and macrophages are increased in the OA synovium compared to normal and pre-OA

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Summary

Introduction

Osteoarthritis (OA) is a degenerative joint disorder that affects all tissues in synovial joints [1,2,3]. Risk factors for OA include age, obesity, and previous joint trauma; the interactions among these factors is unknown [6,7,8,9] Another tissue commonly affected in the pathogenesis of OA is the synovium. Synovium is the soft tissue lining the spaces of diarthrodial joints and contains highly metabolically active cells called synoviocytes that are further separated as macrophage-like (Type A) and fibroblast-like (Type B) synoviocytes These cell types and the synovium as a whole play a key role in normal joint physiology as they facilitate nourishment for chondrocytes and the removal of waste products through the synovial fluid [10]. Because of the synovium’s influential role in maintaining the health of the joint, it is thought that this chronic inflammation of the synovium (and/or alternation of normal synovial function) is detrimental to the overall health of the joint itself

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