Another trial investigated the association between statin therapy initiation and incidence of hand OA, but no association was observed in this study 43

Another trial investigated the association between statin therapy initiation and incidence of hand OA, but no association was observed in this study 43. more likely benefit from a specific drug or cell-based therapy. Current clinical trials addressed mainly regeneration/repair of cartilage and bone defects or targeted pro-inflammatory mediators by intra-articular injections of drugs and antibodies. Pain was treated mostly by antagonizing nerve growth factor (NGF) activity and its receptor tropomyosin-related kinase A (TrkA). Therapies targeting metabolic disorders such as diabetes mellitus and senescence/aging-related pathologies are not specifically addressing OA. However, none of these therapies has been proven to modify disease progression significantly or successfully prevent Mmp2 final joint replacement in the advanced disease stage. Within this review, we discuss the recent advances in phenotype-specific treatment options and evaluate their applicability for use in personalized OA therapy. studies resulted in positive effects on the joint and confirmed the effectiveness of EV injections as a minimally invasive therapy 56. Exosome injections partially improved the gait abnormality patterns in an OA mouse model 57, and MSC secretome injections provided early (day seven) pain reduction in treated mice 58. All together, these data support the translational potential of this regenerative approach. The promising and results support the potential of this new treatment strategy, Fas C- Terminal Tripeptide opening up new perspectives for cell component-based therapies. EVs Fas C- Terminal Tripeptide are proposed as next-generation biomarkers to predict the pathophysiological state of the joint 55, assigning an important role for EVs in future therapies for the treatment of joint disorders. Remarkably, they constitute a simpler, and most of all safer, alternative to actual cell-based therapeutic strategies, as they are cell derived but not living cells and thus cannot proliferate or form tumors. As known for cells, EVs can also be combined with scaffolds, either bound on their surface or embedded within the biomaterial matrices. Specific activation signals such as ultrasound may enable the controlled release of specific subpopulations of EVs, i.e. exosomes. Therapies addressing subchondral bone Besides nutrient supply and metabolism, physiological and non-physiological shock absorption and support of overlying cartilage are the main functions of subchondral bone 59, 60. Therefore, any changes affecting bone cell metabolism, structural integrity, and architecture might render the bone more susceptible to aberrant loading or even induce abnormal reactions to normal physiological load. OA-related changes in subchondral bone structure were long regarded as an adaptation of bone to the biomechanical changes observed in articular cartilage. Recently, several pre-clinical and clinical studies demonstrated that alterations in bone structure might even precede and instead mediate cartilage pathology 61, 62 and that OA progression is associated with temporal changes in bone structure 60. In early OA, accelerated bone turnover leads to bone plate thinning and increased porosity, whereas the trabecular compartment shows increased trabecular spacing and decreased bone volume fraction. Progression of OA is accompanied by subchondral bone plate thickening, increased trabecular thickness, and increased bone volume fraction 60. Bone marrow lesions (BMLs), a hallmark of OA, appear early on MRI and are associated with increased pain and cartilage degeneration 63. Therapies with bisphosphonates Bisphosphonates (BPs) effectively slow down bone turnover by inhibiting osteoclast activity in Fas C- Terminal Tripeptide osteoporosis, but their usability in OA remains uncertain 18. There are indications that a specific patient subgroup might respond to BP use: intravenous zoledronic acid successfully reduced BML size and visual analogue scale (VAS) pain score after 6 months in a randomized controlled trial, though a second multicenter trial could not confirm the results 16, 17. Furthermore, a meta-analysis by Vaysbrot reason why patients see a physician. Huge effort has been put into OA-related pain research to identify underlying mechanisms, but, because of its complexity, no general guidelines could be identified for its effective treatment 97, 98. The sensation of pain in OA does not show uniform appearance among patients and during progression. The source of OA pain includes nociceptive pain komma inflammatory pain and neuropathic pain as well as processes of Fas C- Terminal Tripeptide peripheral and Fas C- Terminal Tripeptide central sensitization. Structural features like BMLs, synovitis, and joint effusion show a strong association with pain intensity 63, 99, 100. Classical treatments include the use of acetaminophen (paracetamol), NSAIDs, and opioids, which induce a plethora of unwanted side effects. Here komma we will discuss the latest developments in therapies directly.