GINS2 affects activity/differentiation, apoptosis and proliferation of osteoblast and osteoclast in steroid-induced osteonecrosis of the femoral head by regulating P53/GADD45A signaling pathway

Abstract

To investigate the function and mechanism of GINS complex subunit 2 (GINS2) in osteoblast and osteoclast in steroidinduced osteonecrosis of the femoral head (SINFH). Clinical specimens were collected from 40 cases of SINFH patients and 40 cases of control patients. Then, SINFH mouse model was built. Immediately, osteoblasts and osteoclasts were induced and differented from the pre-osteoblast cell line MC3T3-E1 and the mononuclear macrophage cell line RAW264.7 of mice, respectively. The qRT-PCR assay was used for detecting the expressions of GINS2, p53 and growth arrest and DNA damage 45A (GADD45A). The cytoactive, proliferation and apoptosis of osteoblasts and osteoclasts of SINFH mice were measured by tartaric acid phosphatase staining, CCK-8 and Annexin V-FITC/PI dual staining, respectively. GINS2 was up-regulated while p53/GADD45A was down-regulated in femoral tissues in SINFH patients and mice. GINS2 was down-regulated while p53 and GADD45A were up-regulated in osteoblasts of SINFH mice, which presented opposite trends in osteoclasts formations. GINS2 decreased osteoblasts activities and increased osteoclasts activities, inhibited apoptosis and promoted proliferation in osteoblasts and osteoclasts via p53/GADD45A pathway. GINS2 affects activity/differentiation, apoptosis and proliferation of osteoblast and osteoclast in steroid-induced osteonecrosis of the femoral head by regulating p53/GADD45A signaling pathway.

Total flavonoids from Lagerstroemia speciosa (L.) Pers inhibits TNF-α-induced insulin resistance and inflammatory response in 3T3-L1 adipocytes via MAPK and NF-кB signaling pathways

“…According to the former studies, the qRT-PCR assay was performed with proper modifications (Tian et al, 2022). The total RNA of 3T3-L1 adipocytes was extracted by Trizol reagent (Invitrogen, Carlsbad, USA) following the manufacturer's protocols.…”

Lactobacillus casei enhances the apoptosis inducing effect of geniposide on U87 human glioma cells in vitro

“…Cancer and conditions associated to cancer frequently include loss of p53 activity. The p53 gene or the p53-regulated network can be altered to influence genomic stability, tumor development, anticancer treatment, and angiogenesis (Tian et al, 2022). The expression levels of target genes implicated in cell cycle arrest, apoptosis, senescence, and anti-angiogenesis can be increased in response to cellular stress programs and activation of the p53 pathway, preventing the transformation of malignant tumors.…”