Neuromedin B Promotes Chondrocyte Differentiation of Mesenchymal Stromal Cells via Calcineurin and Calcium Signaling

Abstract

Background: Articular cartilage is a complex tissue with poor healing capacities. Current approaches for cartilage repair based on mesenchymal stromal cells (MSCs) are often disappointing because of the lack of relevant differentiation factors that could drive MSC differentiation towards a stable mature chondrocyte phenotype. Methods: We used a large-scale transcriptomic approach to identify genes that are modulated at early stages of chondrogenic differentiation using the reference cartilage micropellet model. Results: We identified several modulated genes and selected neuromedin B (NMB) as one of the early and transiently modulated genes. We found that the timely regulated increase of NMB was specific for chondrogenesis and not observed during osteogenesis or adipogenesis. Furthermore, NMB expression levels correlated with the differentiation capacity of MSCs and its inhibition resulted in impaired chondrogenic differentiation indicating that NMB is required for chondrogenesis. We further showed that NMB activated the calcineurin activity through a Ca++-dependent signaling pathway. Conclusion: NMB is a newly described chondroinductive bioactive factor that upregulates the key chondrogenic transcription factor Sox9 through the modulation of Ca2+ signaling pathway and calcineurin activity.

Bioinformatics Analysis Identified miR-584-5p and Key miRNA-mRNA Networks Involved in the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells

“…NRG1 is one of four proteins in the neuregulin family that act on the EGFR family of receptors. It was decreased during BMSCs chondrocyte differentiation ( Maumus et al, 2020 ). Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily and was reported to mediate osteogenic differentiation of BMSCs ( Peyton, 2017 ).…”