# Osteoarthritis--The Role of Mesenchymal Stem Cells in Cartilage Regeneration
## 3 Treatment of OA
### Drug Therapy  
Pharmaceutical approaches are routinely employed when non-pharmacogical measures fail to alleviate pain and reduce disability [82]. The focus of pharmacological treatment for OA is pain management. Medications such as acetaminophen (paracetamol), non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and corticosteroids are often used to relieve pain. However, these drugs do not work long-term and have harmful side effects [83]. Acetaminophen is considered the first line of therapy for mild to moderate OA by OARSI and AAOS [84]. In addition, the use of acetaminophen has been connected to gastrointestinal (GI) adverse effects and multi-organ insufficiency [85], with minimal short-term benefit [86]. NSAIDs have been used for an extended period in the treatment of moderate to severe OA owing to their therapeutic effects in reducing inflammation and alleviating pain. NSAIDs function by inhibiting the enzymes COX-2 and COX-1, both involved in prostaglandin production [87]. Because NSAIDs produce GI side effects, they should be taken with a GI protectant [88]. NSAIDs have also been linked to an increased risk of cardiovascular disease [89]. Although topical NSAIDs prevent gastrointestinal side effects, they are less effective and have been linked to dermatological side effects [90, 91]. In cases where NSAIDs and acetaminophen were ineffective or were deemed unsuitable due to contraindications, opioids such as oxycodone, morphine, or tramadol were used as a means of managing pain of moderate to severe intensity [87]. On the other hand, their long-term efficacy is limited [91], and they have been linked to side effects, including respiratory depression, opioid use disorder, and overdose [91, 92]. As an alternative treatment method for OA of the knee and hip, intra-articular injections of glucocorticoid and hyaluronic acid (HA) are recommended by OARSI [87]. When oral analgesics and anti-inflammatory drugs have not been effective in treating moderate to severe pain in a patient, an intra-articular injection may be considered a potential alternative treatment option. It appears that intra-articular injections of steroids are only successful in studies that last for a limited period, typically no longer than two weeks [91, 93]. Supplementing with HA has been shown to reduce the symptoms of OA [94] by enhancing the function of synovial fluid [95]. The administration of platelet-rich plasma (PRP) through intra-articular injection is a viable and potentially efficacious therapeutic approach for OA. PRP consists of a diverse array of tissue growth factors, such as transforming growth factor (TGF), platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF). These growth factors promote various biological processes, including chondrogenesis, angiogenesis, epithelial cell proliferation, osteoblast proliferation, and fibroblast proliferation. PRP was used to heal tissue, resulting in permanent pain alleviation and functional improvement [96]. Duloxetine is a Food and Drug Administration (FDA)-approved serotonin-norepinephrine reuptake inhibitor to decrease pain and improve function in osteoarthritic knee patients [94]. Capsaicin, a naturally occurring molecule found in chili peppers, is a topical anesthetic [95]. By enhancing proteoglycan formation in joint cartilage, glucosamine and chondro are useful in lowering joint swelling and discomfort, increasing joint flexibility, and improving function [97]. Because existing treatments for OA are not very effective and come with a wide range of unwanted side effects. There is a significant demand for innovative drugs to treat this condition. Inducers of chondrogenesis, inhibitors of matrix breakdown, apoptotic inhibitors,osteogenesis inhibitors, and anti-inflammatory cytokines are some of the therapeutic targets that new drugs aim for [98; 99].