Rácz Kálmán, Segal Yonatan, Lénárt Kinga, Fillér Csaba, Tóth Anna, Szegeczki Vince, Gergely Péter, Zákány Róza, Reglődi Dóra, Juhász Tamás
Department of Forensic Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4032, Debrecen, Hungary.
Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4032, Debrecen, Hungary.
Geroscience. 2025 May 14. doi: 10.1007/s11357-025-01689-4.
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.
垂体腺苷酸环化酶激活多肽（PACAP）是一种在神经系统以及包括肌肉骨骼系统在内的各种外周组织中表达的神经肽。PACAP在软骨形成的调节中具有重要作用，并且在软骨氧化和机械应激中发挥保护作用。PACAP基因敲除（KO）小鼠在膝关节关节软骨中表现出早期衰老和骨关节炎的迹象。其特异性最强的受体是PAC1受体，该受体的激活会导致Sox9表达增强，随后增加II型胶原蛋白、糖胺聚糖和聚集蛋白聚糖的表达。在本研究中，我们调查了取自不同年龄尸体的人膝关节的关节软骨。膝关节关节软骨的厚度和细胞外基质含量随年龄增长而降低。软骨退变过程最可能始于40至50岁之间。PAC1受体的表达随着软骨厚度的减少而平行降低，导致随后软骨特异性基质产生时Sox9表达降低。总之，我们发现软骨厚度和质量的降低与PAC1受体的表达及活性之间存在相关性。
