Possible pathogenetic features of the development and progression of osteoarthritis in the metabolic syndrome (diabetes mellitus, obesity, arterial hypertension)
Authors: Khristich T. M. 
Published: December 2023

The paper emphasizes the pathogenetic features of osteoarthritis in the metabolic syndrome (type 2 diabetes, obesity, and arterial hypertension), such as the violation of the structure of the bone and cartilage tissue of the joints. Attention is paid to such mechanisms as oxidative stress, low-grade chronic systemic inflammation, and participation of the cartilage extracellular matrix, where matriline-3 protein plays an important role. It is involved in cartilage development and possible pathological mechanisms contributing to the onset and progression of osteoarthritis/osteoarthritis.

The significance of abnormal levels of reactogenic forms of oxygen, superoxide anion, and nitrogen monoxide, which provide an increase in the level of peroxynitrite, hydrogen peroxide, myeloperoxidase, and hypochlorous acid, is discussed in detail. It is indicated that in the presence of iron and hydrogen peroxide, chondrocytes release hydroxyl radicals that react with unsaturated fatty acids of membranes and start a chain reaction, producing radicals with a long lifetime. This causes degradation of both the cellular and intercellular components of the cartilage. In addition, intra-articular connections are formed, and the vascular wall is restructured, leading to impaired microcirculation in bone and cartilage tissue due to damage to the vascular endothelium, vasospasm, increased blood clotting, the formation of microemboli, and venous occlusion. As a result, ischemia of the subchondral bone develops, along with damage to the cartilage tissue and a local disturbance of microcirculation. The thickness of the subchondral bone decreases due to angiogenesis at the junction of the articular hyaline cartilage and adjacent subchondral bone in patients with osteoarthritis. This process enhances degenerative-inflammatory changes in the structure of the cartilage due to a violation of metabolic processes in it.

The importance of lipid and protein peroxidation in the regulation of intracellular calcium homeostasis and the ability of smooth muscles to undergo persistent contractions, which cause muscle pain, are emphasized. Pathogenetically, an important role in this process is played by the inhibition of calcium-ATPase in the sarcoplasmic reticulum, the activation of calcium flow through calcium channels, and an increase in intracellular calcium. Hypocalcemia and hypercalciuria in patients with metabolic syndrome contribute to the progression of not only osteoarthritis but other components of the syndrome.

Attention is drawn to the significance of the cytokine link as an important mechanism for the onset and progression of osteoarthritis/osteoarthritis. The features of the reaction of chronic systemic inflammation with the participation of IL-18 and IL-10 in the structure of the extracellular matrix of cartilage, where matrilin-3 protein plays an important role since it is involved both in the development of cartilage and in the progression of osteoarthrosis, depending on multimorbidity with other components of metabolic syndrome, are highlighted.