© Jennifer García Cabello
Bone cell populations interact through both direct contact and paracrine signalling. In this context, the mesenchymal stem cell (MSC) secretome plays a fundamental role in maintaining bone homeostasis. It consists of more than 1,500 proteins, nucleic acids, and metabolites that influence the surrounding microenvironment. However, recent studies have shown that the MSC secretome significantly changes under pathological conditions such as osteoporosis. Nevertheless, little is known about the impact of secretomes from osteoporotic MSCs on the function of healthy MSCs or other bonerelated cells.
In this project, 15 independent conditioned media samples were generated from MSCs isolated from patients subjected to hip replacements due to an osteoporotic fracture (OPhMSCs-CM). Their effects were evaluated in healthy MSCs (ASC52Telo cell line) and osteoblasts (OB52Li cell line), and compared with the effects of a control conditioned media derived from ASC52Telo cells.
The osteogenic potential of ASC52Telo cells was reduced following treatment with OPhMSCs-CM, with impaired mineralisation and alkaline phosphatase activity. In parallel, ROS levels were significantly increased, and chemotactic migration was enhanced. In OB52Li cells, OPhMSCs-CM increased proliferation and oxidative stress, while downregulating key factors for maintaining a homeostatic bone remodelling process OPG, VEGF and CSF.
Untargeted metabolomics revealed the enrichment of senescence- and stress-related metabolites such as thymine, N(1)-acetylspermidine, and HIAA, alongside decreased levels of DL-lactic acid, supporting a dysfunctional redox and differentiation profile. Altogether, these results suggest that secretomes from osteoporotic MSCs exert deleterious paracrine effects on bone niche cells, contributing to a microenvironment les favourable for osteogenesis and tissue repair.
