# Osteoarthritis--The Role of Mesenchymal Stem Cells in Cartilage Regeneration
## 1 Introduction  
Osteoarthritis (OA) is the most prevalent form of chronic joint disease and the leading cause of joint pain, function loss, and disability. In 2020, it was anticipated to be the fourth leading cause of invalidity worldwide. OA is a common degenerative joint condition characterized by cartilage loss and bone proliferation [1, 2]. The extended duration of damage experienced by individuals with osteoarthritis (OA) makes it a prominent contributor to disability. Those with severe OA often suffer from persistent pain and functional limitations in their limbs, leading to a diminished quality of life. Although OA is commonly associated with aging, there are several controllable and non-modifiable risk factors for its occurrence [3]. Over the last decade, the frequency of OA has reportedly quadrupled in men and doubled in women [4]. The prevalence is estimated to be between 10 and 15 percentworldwide, with greater rates among women. Recent estimates indicate that by 2050, over 20% of the global population will be over 60 years old. By 2050, 130 million individuals worldwide will suffer from OA, and 40 million will be severely disabled [5; 6]. OA primarily affects the knee joint, making it the predominant location of pathology with a prevalence of roughly 85 percent worldwide. The hand and hip are the following most common sites afflicted [7; 8; 9]. OA is characterized by structural alterations in several components of the joint, including joint cartilage, subchondral bone, ligaments, synovium, and periarticular muscles. Degeneration of the extracellular matrix (ECM) is responsible for the clearest arthritic condition, joint cartilage deficiency. Individuals with OA experience physical weakness, mental stress, and a decline in quality of life [5; 10; 11]. The frequency of OA varies geographically and ethnically. Asian and Eastern groups have a low frequency of hip OA, but African Americans are more prone to developing symptomatic OA of the knee [10; 1]. According to etiology, OA may be classified into two distinct categories: primary and secondary. The etiology of primary OA remains elusive. Secondary OA can arise due to several factors, including an underlying illness, inflammation, infection, deformity, or injury [12]. Primary OA is related to aging and typically affects older adults; it is an idiopathic phenomenon that affects previously healthy joints and has no known cause. Secondary OA is a disease of the synovial joints caused by a predisposing condition that negatively impacts the joint tissues. Moreover, secondary OA can occur in relatively youthful individuals [13]. Secondary OA may arise from several causes, such as congenital disabilities affecting the joints at birth, recurrent joint surgeries or trauma causing damage to joint structures, metabolic problems (ochronosis, microcrystalline arthritis, Wilson's disease), endocrine diseases (acromegaly, diabetes mellitus, hyperparathyroidism, hypothyroidism), and inflammatory arthritis, such as rheumatoid arthritis (RA), ankylosing spondylosis, reactive arthritis, psoriasis, gout, pseudogout, and ulcerative colitis [12; 14; 15]. Mesenchymal stem cells (MSCs), a distinct category of adult stem cells, show significant promise in bone tissue engineering and regenerative treatment, mainly attributed to their inherent ability to undergo self-renewal and differentiation. Intra-articular injections of MSCs have shown improvements in the knee joint's structure, pain, and function, thereby establishing them as a potentially practical and innovative therapeutic approach for OA [16]. MSCs, widely dispersed in many tissues such as the bone marrow, periosteum, trabecular bone, fat pad tissue, and synovial membrane, have significant capabilities in facilitating chondrocyte regeneration and undergoing cartilage differentiation [16]. Autologous cells may be obtained from patients via two methods: liposuction or aspiration from bone marrow [17]. MSCs and their exosomes have been found to perform various functions in treating OA.