Molecular-Morphological Relationships of the Scaffold Protein FKBP51 and Inflammatory Processes in Knee Osteoarthritis.

Fabián Poletti,Ali Mobasheri,Julio Ávila,Pablo Martín-Vasallo,Deborah Rotoli,María-Del-Pino García,Rebeca González-Fernández

doi:10.3390/cells10092196

Abstract

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions affecting the adult population. OA is no longer thought to come from a purely biomechanical origin but rather one that has been increasingly recognized to include a persistent low-grade inflammatory component. Intra-articular corticosteroid injections (IACSI) have become a widely used method for treating pain in patients with OA as an effective symptomatic treatment. However, as the disease progresses, IACSI become ineffective. FKBP51 is a regulatory protein of the glucocorticoid receptor function and have been shown to be dysregulated in several pathological scenario’s including chronic inflammation. Despite of these facts, to our knowledge, there are no previous studies of the expression and possible role of FKBP51 in OA. We investigated by double and triple immunofluorescence confocal microscopy the cellular and subcellular expression of FKBP51 and its relations with inflammation factors in osteoarthritic knee joint tissues: specifically, in the tibial plateau knee cartilage, Hoffa’s fat pad and suprapatellar synovial tissue of the knee. Our results show co-expression of FKBP51 with TNF-α, IL-6, CD31 and CD34 in OA chondrocytes, synovial membrane cells and adipocytes in Hoffa’s fat pad. FKBP51 is also abundant in nerve fibers within the fat pad. Co-expression of FKBP51 protein with these markers may be indicative of its contribution to inflammatory processes and associated chronic pain in OA.

Highlights

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions in the adult population worldwide, affecting over 80% of the population beyond the age of 55 [1]
Our results show co-expression of FK506-binding protein 51 (FKBP51) with tumor necrosis factor α (TNF-α), IL-6, CD31 and CD34 in OA chondrocytes, synovial membrane cells and adipocytes in Hoffa’s fat pad
Co-expression of FKBP51 protein with these markers may be indicative of its contribution to inflammatory processes and associated chronic pain in OA

Summary

Introduction

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions in the adult population worldwide, affecting over 80% of the population beyond the age of 55 [1]. OA is no longer considered as a purely mechanical process but rather one that has been increasingly recognized to include chronic and persistent low-grade inflammation [7] This is thought to be the result of the imbalance between pro and anti-inflammatory mediators that induce extracellular matrix (ECM) degeneration and chondrocyte apoptosis, subchondral bone remodeling, osteophyte formation, inflammatory infiltration of the synovial tissues and the infrapatellar fat pad, as well as neo angiogenesis and nerve invasion of the articular cartilage and menisci [8,9]. CD31, CD34, and Iba were selected as markers for endothelial, pluripotential, or macrophage cells in order to check angiogenesis, linking progenitor and adult stem cell phenotypes and microenvironmental cells involved in inflammation, respectively [12,13,14]

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