Circulating and Synovial Fluid Heat Shock Protein 70 Are Correlated with Severity in Knee Osteoarthritis

Abstract

Objective Heat shock proteins are molecules rapidly produced under conditions of environmental stress, and involve in protecting the cells structural integrity and function. Osteoarthritis (OA) is a chronic destructive disorder of the joints manifested by the ongoing deterioration and loss of articular cartilage. The present study aimed to analyze circulating and synovial heat shock protein (Hsp70) values in knee osteoarthritis patients and healthy controls and to determine their relationship with the radiographic grading of the severity of knee OA. Design Seventy-two subjects with knee OA and 30 control participants were recruited. Circulating and joint fluid Hsp70 values were quantified by commercially available enzyme-linked immunosorbent assay. Results Circulating Hsp70 was markedly higher in knee OA patients compared with that of healthy volunteers ( P = 0.01). Correspondingly, synovial fluid Hsp70 was 3-fold greater than paired circulating Hsp70 samples ( P < 0.001). Further analysis revealed that circulating and joint fluid Hsp70 values were significantly related with the radiographic severity of knee OA ( r = 0.413, P < 0.001 and r = 0.658, P < 0.001, respectively). Subsequently, circulating Hsp70 value was directly associated with joint fluid Hsp70 value ( r = 0.704, P < 0.001). Conclusions Circulating and synovial Hsp70 levels were positively correlated with the radiographic severity of knee OA. Hsp70 could represent a potential biochemical marker for predicting the severity and may play a fundamental part in the pathogenic mechanism of knee OA.

Synovial tissue from sites of joint pain in knee osteoarthritis patients exhibits a differential phenotype with distinct fibroblast subsets

“…2). Interestingly, serum and synovial fluid concentrations of HSP70 (encoded by HSPA1A), correlate with knee OA severity [19] and are increased in synovial fibroblasts from RA-diseased joints [20] . End-stage OA pain fibroblasts also exhibited high expression of HTRA3, a serine proteinase implicated in the degradation of extracellular matrix [21] , which could indicate that these cells also mediate cartilage destruction as disease progresses.…”

Expression pattern of Syndecan-1 and HSP-70 in hip tissue of patients with osteoarthritis

“…12 Furthermore, in 2018 Ngamurkos et al came to the conclusion that HSP-70 levels in human knees were increased according to their disease severity and that it could be used as a biomarker for the prediction of OA severity. 7 Nevertheless, HSP-70 overexpression alone might not be sufficient in protection of cartilage. 9 According to Siebelt et al, HSP-90 might play a bigger role.…”

“…6 HSP-70 belongs to the family of Heat shock proteins. 7 Its physiologic role is to protect the structural integrity and cellular proteins by inhibiting multiple pathways of apoptosis, such as Nitric Oxide induced caspase 3, the previously mentioned NF-κB, JNK, apoptosome formation and mitochondrial cytochrome C release. [7][8][9][10] Moreover, it protects the cells from oxidative stress which otherwise would result in apoptosis and necrosis.…”

“…7 Its physiologic role is to protect the structural integrity and cellular proteins by inhibiting multiple pathways of apoptosis, such as Nitric Oxide induced caspase 3, the previously mentioned NF-κB, JNK, apoptosome formation and mitochondrial cytochrome C release. [7][8][9][10] Moreover, it protects the cells from oxidative stress which otherwise would result in apoptosis and necrosis. 7 Furthermore, it has been researched in rats, when exposed to different severities of exercise, that little and intermediate workout increased HSP-70 expression actually preventing OA by promoting cell metabolism to provide enough sulfated glycosaminoglycan to the ECM in the joint.…”

“…[7][8][9][10] Moreover, it protects the cells from oxidative stress which otherwise would result in apoptosis and necrosis. 7 Furthermore, it has been researched in rats, when exposed to different severities of exercise, that little and intermediate workout increased HSP-70 expression actually preventing OA by promoting cell metabolism to provide enough sulfated glycosaminoglycan to the ECM in the joint. 9 However, severe exercise resulted in OA despite increased HSP-70 potentially exceeding its capacity of protection.…”