[Chondrocytes secretory phenotype associated with aging: role in the pathogenesis of osteoarthritis and prospects for peptide bioregulation.]

Osteoarthritis (OA) is a socially significant age-associated disease, for the treatment of which a search for new effective drugs is underway. The development of OA correlates with the development of the aging-associated secretory chondrocyte phenotype (SASP). The purpose of the review is to analyze the pool of signaling molecules that form SASP of chondrocytes in OA and substantiate the possibility of peptide chondroprotection. It has been established that SASP of chondrocytes is characterized by a decrease in the synthesis of sirtuins, impaired remodeling of the extracellular matrix, and activation of cytokine production. Sigumir, a polypeptide complex of cartilage and bone tissues of young animals, and the AED tripeptide (Kartalax) have shown high efficacy in animal models of OA and oral administration in patients with OA of older age groups. These peptide substances regulate the synthesis of proapoptotic and proliferotropic molecules that form the SASP of chondrocytes.

[The influence of peptides on the chondrogenic differentiation of human mesenchymal stem cells during replicative aging.]

Osteoarthritis is a widespread age-related disease, that has no effective targeted therapy. In this regard, bioengineering methods are being actively developed that can stimulate the restoration of cartilage tissue. These methods include chondrogenic differentiation of stem cells, which is stimulated by various biomolecules, including short peptides and polypeptide complexes. It was studied the effect of the cartilage polypeptide complex (CPC) and AED peptide on gene expression and protein synthesis of chondrogenic differentiation - SOX9, aggrecan, type II collagen and COMP - in human mesenchymal stem cell (MSC) during replicative aging. AED peptide at the concentration of 200 ng/ml activates gene expression and protein synthesis during aging of MSCs. CPC has the same effect in the concentration 2000 ng/ml. These data indicate the stimulating effect of studied peptides on regulation of chondrogenesis and open up prospects for further investigation of their effectiveness in osteoarthritis models.

[Peptides prevent the forming of secretory phenotype of chondrocytes associated with the aging.]

Secretory phenotype associated with the aging (SASP) of chondrocytes forms the conditions for the musculoskeletal system diseases development, in particular, osteoarthritis (OA). The search for effective methods for OA treating is an urgent task of molecular gerontology. The purpose of this work is to characterize the SASP of chondrocytes and to conduct a comparative assessment of the effect of AED peptide and the cartilage polypeptide complex (CPC). It was found that chondrocyte's SASP is characterized by an increase of the synthesis of p16, p21, p53 pro-apoptotic proteins, TNF-α, IL-1α pro-inflammatory cytokines and a decrease of Sirt1synthesis. Peptides AED and CPC normalize the synthesis of molecules that form SASP of chondrocytes. This effect may explain their geroprotective effect and effectiveness in studies of various pathologies of the musculoskeletal system, including OA.