Ca2+/Mg2+ homeostasis-related TRPM7 channel mediates Chondrocyte hypertrophy via regulation of the PI3K-Akt signaling pathway

Abstract

Chondrocytes are specialized cells that form cartilage tissue, and are able to respond to their osmotic environment and exercise important roles in endochon-dral ossification via undergoing proliferation, hypertrophy and apoptosis. The transient receptor melastatin potential 7 (TRPM7) cation channel can modulate the intracellular and extracellular levels of Ca2+ and Mg2+, and therefore the cellular osmotic environment. However, the molecular pathways involved in TRPM7-mediated signal transduction have yet to be elucidated. In the present study, the expression and functionality of TRPM7 were investigated during chondrocyte proliferation and hypertrophy. The ATDC5 mouse cell line was employed and cellular viability was evaluated using the MTT assay, whereas hypertrophy was monitored via evaluating the expression of chondrogenic marker genes and the activity of alkaline phosphatase (ALP). Gene expression of TRPM7 appeared slightly upregulated during the proliferative stages of chondrocyte development, and significantly upregulated during the hypertrophic stages, suggesting the importance of Ca2+/Mg2+ homeostasis for chondrocyte growth. Low extracellular Ca2+/Mg2+ levels significantly reduced the expression of type X collagen, Indian hedgehog homolog (Ihh) and matrix metalloproteinase (MMP)-13 genes, as well as ALP activity; however, cell viability remained unaffected. Conversely, the.