Osteoarthritis (OA) mostly occurs in older adults. Its incidence rate in China is approximately 17% in the middle-aged population, with higher prevalence in women [1, 2]. This disease commonly affects the weight-bearing joints, with knee osteoarthritis (KOA) accounting for > 80% of all OA cases [3, 4]. KOA manifests as sclerosis of the subchondral bone and periarticular cartilage, in addition to the wear and tear, degeneration, softness, deformation, and disappearance of the articular cartilage. Sclerosis of the subchondral bone, periarticular synovial hyperplasia, degeneration and atrophy of the joint capsule, peripheral ligaments, and other tissues, destruction of the integrity of the joint surface, and narrowing of the joint space can lead to knee deformity [5, 6]. Pathological changes mainly occur in the synovial membrane, cartilage, meniscus, and patella in the early stages of KOA [7], while knee joint pain, stiffness, swelling, limited activity, popping, and deformity appear gradually. KOA can involve the muscles, seriously affecting patients’ physical and mental health and daily activities [8]. Therefore, early diagnosis, intervention, and treatment have become the focus of joint surgeries.
Cartilage wear and tear is the core pathological change in KOA; however, pathological cartilage changes occur in the middle and late stages [9]. Synovial inflammation, an important early pathological change in KOA, can result in knee pain and structural changes, and its incidence has been increasing continuously [10]. Normal synovial and cartilage tissues are loose connective tissues that secrete synovial fluid to nourish the cartilage, reduce friction, maintain intra-articular metabolism, and provide nutrition to the articular cartilage [11, 12]. Intra-articular lesions lead to the loss of synovial nutritional function and production of many proteases and cytokines, damaging the chondrocytes. The pro-inflammatory factors released from synovial and cartilaginous tissues stimulate the production of protein hydrolyzing enzymes, thereby aggravating articular cartilage degeneration, which causes joint pain and deterioration [13–16].
Ras homolog gene family member A (RhoA) proteins are expressed in all tissues and affect cell growth, transformation, cytoskeletal regulation, actin stress fiber formation, and actin-myosin contraction [17–19]. Rho-associated protein kinase (ROCK), a downstream effector of RhoA, exists as two isoforms, ROCK1 and ROCK2. The RhoA/ROCK signaling pathway is involved in cell growth, differentiation, migration, and development [20, 21], and is required for neuronal synaptic growth, bone formation, dorsal closure, and myogenesis [22]. Its aberrant activation is associated with various cancer types and diseases affecting the neurological, endocrine, and cardiovascular systems [23–28]. Previous studies have shown that the RhoA/ROCK signaling pathway is closely related to cartilage degeneration in KOA, but such association has not been studied in synovial lesions in KOA.
The aim of this study was to investigate the correlation between the RhoA/ROCK signaling pathway and the pathogenesis of KOA by comparing the expression of RhoA and ROCK in the synovial tissue of patients with primary KOA as a way to potentially identify a therapeutic target for delaying synovial lesions in KOA.