Cartilage degradation is followed by PAC1 receptor reduction in articular cartilage of human knee joints

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide expressed in the nervous system and also in various peripheral tissues, including the musculoskeletal system. PACAP has an important function in the regulation of chondrogenesis and plays a protective role in cartilage oxidative and mechanical stress. PACAP knockout (KO) mice show early signs of aging and osteoarthritis in knee joint articular cartilage. Its specific, most potent receptor is the PAC1 receptor, the activation of which leads to enhanced Sox9 expression and subsequently, it increases the expression of collagen type II, glucosaminoglycans and aggrecan. In the present study, we investigated articular cartilage of human knee joints taken from cadavers of varying ages. Thickness and extracellular matrix content of articular cartilage of knee joints decreases with aging. The cartilage degeneration process most likely begins between the ages of 40 to 50. Expression of PAC1 receptor decreases in parallel with the reduction of cartilage thickness, leading to subsequent reduced Sox9 expression with cartilage specific matrix production. In summary, we found correlation in the reduction of cartilage thickness and quality together with PAC1 receptor expression and activity.