软骨细胞
细胞生物学
蛋白激酶B
TRPM7型
生物
信号转导
PI3K/AKT/mTOR通路
软骨内骨化
细胞生长
化学
软骨
生物化学
瞬时受体电位通道
受体
解剖
作者
Daigang Lu,Jining Qu,Liang Sun,Qiang Li,Lei Hua,Na Yang,Teng Ma,Qian Wang,Ming Li,Kun Zhang,Li Zhong
出处
期刊:Molecular Medicine Reports
[Spandidos Publications]
日期:2017-08-21
卷期号:16 (4): 5699-5705
被引量:15
标识
DOI:10.3892/mmr.2017.7300
摘要
Chondrocytes are specialized cells that form cartilage tissue, and are able to respond to their osmotic environment and exercise important roles in endochondral 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 gene expression levels of TRPM7 appeared upregulated in ATDC5 cells under low extracellular Ca2+ or Mg2+ conditions. Silencing TRPM7 expression during the chondrocyte differentiation period also reduced type X collagen, Ihh and MMP‑13 gene expression, and ALP activity. Furthermore, the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K)‑Akt signaling pathway was activated following TRPM7 overexpression, and inhibited following TRPM7 silencing. Notably, the actions of TRPM7 on chondrocyte hypertrophy were abolished through the inhibition of PI3K‑Akt signaling. The present results suggested that TRPM7 may be involved in Ca2+/Mg2+ homeostasis during chondrocyte hypertrophy, and contribute to endochondral ossification via interacting with the PI3K‑Akt signaling pathway.
科研通智能强力驱动
Strongly Powered by AbleSci AI