Purpose
The treatment of early degenerative processes affecting cartilage could prevent further aggravation and the onset of osteoarthritis (OA). The aim of the present study is to analyze the predicted potential of the micro RNAs (miRNAs) produced by cartilage cells (CCs), adipose- (ASCs) and bone marrow-derived (BMSCs) stem cells as a therapy to treat joint degeneration.Methods and Materials
Articular cartilage, bone marrow and subcutaneous adipose tissue were collected from 3 patients who underwent total hip replacement. Cells were isolated, expanded and the supernatants were differentially centrifuged to obtain extracellular vesicles (EVs). Expression of EV-embedded miRNA were evaluated with the QuantStudio™ 12 K Flex OpenArray® platform. Mientournet and Ingenuity Pathway Analysis (IPA) were used for validated target prediction analysis and to identify miRNAs involved in OA and inflammation.Results
Among the 428 analyzed miRNAs, 325 were expressed by all the cell populations, 26 shared by CCs and ASCs, 21 shared by CCs and BMSCs and 17 shared by ASCs and BMSCs. The miRNA selectively expressed only in one cell population were 16 by CCs, 12 by ASCs and 11 by BMSCs. Mienturnet revealed no results for miRNA selectively expressed by ASCs, whereas for CCs miR-17-3p, miR-25-5p, miR-200c-3p and miR-449a showed the highest number of interactions and putatively modulate cell cycle, senescence, apoptosis, Wnt, TGFβ, VEGF, Notch, Hippo, TNFα and IL-1β signaling. For BMSCs the highest number of interaction was showed by miR-141-3p, miR-143-5p, miR-363-3p, miR-205-5p and miR-483-3p involved in apoptosis, TGFβ, IGF-1, RUNX2 and endochondral ossification pathways. IPA analysis showed that many differently expressed miRNAs regulate macrophages and T cells activity, the expression of inflammatory mediators, cartilage homeostasis and cell proliferation.Conclusion
Despite the need to be validated by functional tests, the predicted pathways identified in this study confirm and support the rationale behind the use of cell-based therapy for the treatment of degenerative joint conditions.
