Wnt3a and wnt5a as Potential Chondrogenic Stimulators for Nucleus Pulposus Cell Induction: A Comprehensive Review

Low back pain remains a highly prevalent pathology engendering a tremendous socioeconomic burden. Low back pain is generally associated with intervertebral disc (IVD) degeneration, a process involving the deterioration of nucleus pulpous (NP) cells and IVD matrix. Scientific interest has directed efforts to restoring cell numbers as a strategy to enable IVD regeneration. Currently, mesenchymal stromal cells (MSCs) are being explored as cell therapy agents, due to their easy accessibility and differentiation potential. For enhancement of MSCs, growth factor supplementation is commonly applied to induce differentiation towards a chondrogenic (NP) cell phenotype. The wnt signaling pathways play a crucial role in chondrogenesis, nonetheless, literature appears to present controversies with regard to wnt3a and wnt5a for the induction of NP cells, chondrocytes, and MSCs. This review aims to summarize the reporting on wnt3a/wnt5a mediated NP cell differentiation, and to elucidate the mechanisms involved in wnt3a and wnt5a mediated chondrogenesis for potential application as cell therapy supplements for IVD regeneration. Our review suggests that wnt3a, subsequently replaced with a chondrogenic stimulating growth factor, can enhance the chondrogenic potential of MSCs in vitro. Contrariwise, wnt5a is suggested to play a role in maintaining cell potency of differentiated NP or chondrogenic cells.