Biologic basis of osteoarthritis

Abstract

Purpose of Review Evidence accumulated since 2010 indicates that human osteoarthritis should now be reclassified as a systemic musculoskeletal disease rather than a focal disorder of synovial joints. Recent Findings Inflammation was seen as the key component promoting synovitis as well as progression of cartilage and bone destruction in osteoarthritis. Thus, metabolic-triggered inflammation involving cytokines, adipokines, abnormal metabolites, acute phase reactants and even complement, all appear to play major roles in OA pathophysiology. Immune-mediated inflammation involving T- and B-cells as well as macrophages is now considered a common finding in OA synovial tissue. Many experimental and clinical analyses showed that the pro-inflammatory cytokines which stimulate matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motif gene transcription in normal and OA human chondrocyte cultures are also present at significantly elevated levels in the synovial fluid of OA patients compared to non-arthritic synovial fluids. Summary Human osteoarthritis is a systemic musculoskeletal disorder involving activation of innate and adaptive immune systems accompanied by inflammation exemplified by the elevated production of pro-inflammatory cytokines which play a significant role in the progression of the disease. The future of novel therapies for osteoarthritis should consider developing drug development strategies designed to inhibit pro-inflammatory cytokine-induced signal transduction. These strategies have been successful in the development of drugs for the treatment of rheumatoid arthritis.

Evaluation of the anti-inflammatory effects of two platelet-rich gel supernatants in an in vitro system of cartilage inflammation

“…In general, OA is characterized by a catabolic state of the articular cartilage, in which pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-a) and interleukin 1 (IL-1), are up-regulated and they, in turn, induce gene up-regulation and local tissue production of cartilage-associated degradation enzymes as matrix metalloproteinases (MMPs) and nitric oxide synthases (NOSs) and pro-inflammatory substances as prostaglandins, leukotrienes and nitric oxide, which finally produce joint damage and pain [2,4,5].…”

An update on the pathophysiology of osteoarthritis

“…Throughout life, cartilage is continually remodeled as chondrocytes replace the degraded matrix macromolecules with newly synthesized components, although it is recognized that this is an exceptionally slow process in adults; proteoglycan turnover can take up to 2 decades whereas the half-life of collagen is estimated to range from several decades to more than 100 years (20)(21)(22). Although articular cartilage can tolerate a tremendous amount of intensive and repetitive physical stress, it manifests a striking inability to heal even a minor injury (2 (23), it has inflammatory and metabolic components (1,16,(24)(25)(26)(27).…”

Comparison of Bone Tissue Elements Between Normal and Osteoarthritic Pelvic Bones in Dogs

“…It is the most common form of arthritis and often progresses slowly with age. Research on OA has generally focused on understanding the biology, etiology, and pathology of the disease, finding new techniques for early diagnosis, and developing effective treatments to reinitiate proper function of articular cartilage and surrounding tissues [4,5]. Many studies have evaluated articular cartilage mineralization in patients affected with OA; however, investigations of subchondral bone also are warranted.…”