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

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.

FKBP51, AmotL2 and IQGAP1 Involvement in Cilastatin Prevention of Cisplatin-Induced Tubular Nephrotoxicity in Rats

“…FKBP51 is an immunophilin with peptidyl-prolyl cis-trans isomerase (rotamase) activity which acts as a co-chaperone associated with heat shock protein 90 (Hsp90), heat shock protein 70 (Hsp70) and p23; it plays a role in steroid receptor signaling, translocating from the cytosol to either the mitochondria or nucleus, where it modulates pathways involving protein kinase B (Akt), protein kinase A (PKA), nuclear factor-kappa B (NF-κB), transforming growth factor (TGF) and tumor necrosis factor alpha (TNFα) [14][15][16][17][18][19][20]. FKBP51 is abundantly expressed in tumours [21,22] and is involved in antiapoptotic processes in cancer cells [23].…”