Osteoarthritis (OA) is a degenerative disease, and it primarily affects hips and knees as major weight-bearing joints . Over the past two decades, knee osteoarthritis (KOA) has become fastest basis of expanding physical disability with a significant economic burden worldwide [2, 3]. KOA is the most common form of arthritis, and characterized by joint degeneration, loss of cartilage, osteophyte formation, cysts and alterations of subchondral bone [4, 5]. Besides that, a broad range of mechanical and biochemical inflammatory mediators (pro-inflammatory cytokines, growth factors and matrix metalloproteinase) contribute to the pathogenesis of KOA [6, 7]. Till to date, the prime cause of KOA development is still unidentified and optimal treatment remain elusive. Studies shows that more than 40 million Americans having OA, and 80% among them older than 50 years . Other studies shows that knee osteoarthritis prevalence rate in Chinese and Japanese population is also cumulative. The prevalence rate in in Chinese population reached 15.6% in over 40 years aged groups . Beside that the prevalence rate of KOA in Japanese population reported as up to 42.0 % in men and 62.4 % in women over 40 aged groups . Therefore, knee osteoarthritis (KOA) is a global issue in elderly population and early diagnosis is required to begin possible treatment.
Radiography imaging technique is viewed as a gold standard method for diagnosis of KOA, but the current imaging technique is suffering with the sensitivity and specificity . Although, imaging technique allows detection OA of the knee: joint space narrowing, presence of osteophytes, subchondral sclerosis, and cysts. Due to lack of sensitivity and specificity of radiographic imaging technique, there is an urgency to develop a potentially alternative tool for diagnosis of KOA. Body fluid serum routinely tested in clinics for diagnosis, and treatment of different diseases. They are very decisive medium and harbor plenty of biomarker for the monitoring of our health. Earlier basic and clinical studies revealed several biomarkers are known to be correlated with the extent of OA on radiography of the knee and being proposed as diagnostic tools [12–15]. However, the currently used biomarkers are inadequate for prognosis of OA.
The receptor tyrosine kinase AXL is a 140-kDa protein that belongs to a tyrosine kinase receptor (TAM) subfamily, together with Tyro3 and Mer. The TAM receptors (AXL, Tyro3 and Mer) play critical role in innate immune homeostasis and vitamin-K dependent ligand growth arrest specific protein 6 (GAS6) can binds all three receptors with highest affinity for AXL [16, 17]. Transmembrane protein AXL can be cleaved proteolytically at its extracellular membrane domain (EMD) and subsequently released as soluble AXL, which can be detected in serum or plasma [18, 19]. Furthermore, studies revealed that targeted delivery of TAM receptor ligand genes Gas6 diminishes the arthritis pathology effectively but endogenous role of AXL in arthritis development is not fully understood . We hypothesized that AXL concentration is correlated with the severity of KOA and can predict the development and progression of KOA as seen on radiography of the knee.
In the present study, we analyzed AXL levels in sera from participants suffering from KOA and divided in different groups according to the Kellgren-Lawrence (KL) score. We assess the diagnostic performance of AXL for KOA in comparison to participant control groups. Furthermore, we were able to determine the accuracy of AXL in KOA in different groups that demonstrating the potential diagnostic value of AXL for routine clinical use in surveillance of patients at high risk for KOA severity.