Introduction
knee OA, Osteoarthritis, OA, synovial inflammation, knee injury, pain, degenerative disease, overweight, end-stage OA, disability
HAND OSTEOARTHRITIS, TYPE 2 DIABETES, OSTEOARTHRITIS, HAND SWELLING
Osteoarthritis (OA) is a multifactorial progressive degenerative disease that is associated with synovial inflammation and bone remodeling and leads to impaired functional characteristics of the joint cartilage [Racial/ethnic disparities in OA are well-recognized. Several studies have shown that non-Hispanic Black (NHB) individuals experience higher rates of symptomatic and radiographic OA, higher age-related average pain intensity, and higher levels of disability than their non-Hispanic White (NHW) counterparts, in addition to higher pain sensitivity [Bcl-2 is an anti-apoptotic protein that suppresses apoptosis by inhibiting the action of Bcl-2 associated X protein (BAX), a member of the Bcl-2 family that promotes apoptosis via the mitochondrial-mediated pathway. The ratio of Bcl-2 to BAX expression indicates cellular susceptibility to apoptosis [The Bcl-2 polymorphism (-938 C> A, rs2279115), a functional SNP on chromosome 18q21.33, is located in the P2 promoter region. It has been reported that the wild type of this SNP may inhibit gene transcription and thus negatively affect Bcl-2 levels [Various studies have shown that the occurrence and development of OA are closely associated with the abnormal balance between autophagy and apoptosis in the cartilage [CXCL-16 is a chemokine secreted by synovial macrophages and fibroblasts that mediates the chemo-attraction of neutrophils, lymphocytes, and monocytes into the synovium [Metformin is a safe and tolerable oral drug known as the first-line treatment for type 2 diabetes [To date, there has been no effective non-surgical treatment for OA, and existing therapies such as analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are only used to reduce pain and swelling. It is noteworthy that surgical therapy is the last option for patients with end-stage OA [To evaluate the outcome of any therapeutic interventions for knee OA, it is recommended to use multi-item knee-specific outcome measures, such as knee injury and osteoarthritis outcome score (KOOS) to provide a broader picture of the clinical condition [The aim of this study was to assess the effect of metformin versus placebo on symptoms of knee OA in overweight patients diagnosed with knee OA in a randomized, double-blind, placebo-controlled trial in a 4-month period using the KOOS questionnaire. Moreover, considering the role of autophagy, AMPK, and the mTOR pathways in OA as well as the effect of Bcl-2, and CXCL-16 in regulation of the mTOR pathway, we aimed to investigate the role of genetic diversity of Bcl-2 and CXCL-16 in OA.