Articular Cartilage Stem Cells Influence the Postoperative Repair of Hip Replacement by Regulating Endoplasmic Reticulum Stress in Chondrocytes via PERK Pathway.

OBJECTIVE: Endoplasmic reticulum stress (ERS) is present in chondrocytes of osteoarthritis, and the intensity of ERS is related to the degree of cartilage degeneration. In vitro intervention strategies can change the status of ERS and induce the inhibition of ERS-related pathway. Therefore, this study is designed to explore the role and molecular mechanism of cartilage stem cells (ACSCs) of ERS in chondrocytes after hip replacement. METHODS: Human cartilage cell lines C28/I2 were cultured as the control group. The ERS inducer was added into C28/I2 as ERS group. The third ERS + stem cells group was formed by adding cartilage stem cells into ERS group, and further transfection of si-PERK was defined as si-PERK + ERS + stem cells group. Cell cycle and apoptosis in the four groups were determined by flow cytometry. The protein expression of GRP78, PERK, ATF4, TMEM119, CDK4, Cyclin D, and BMP6 in chondrocytes in the four groups were investigated by western blot, and the distribution of PERK, TMEM119, and BMP6 in chondrocytes were observed by immunofluorescence assay. In addition, the transcriptional levels of Bcl2, Bax, and Caspase 3 were also determined by RT-PCR. RESULTS: In cell cycle assay, ERS increased the accumulation of cells in G0 /G1 and G2 /M, while cartilage stem cells weakened the effects. The apoptosis rates in control group, ERS, ERS + stem cells, si-PERK + ERS + stem cells were 0%, 21.3%, 18.9%, and 15.9%, respectively, and the difference of apoptosis rate between the latter three groups and control group was statistically significant (P < 0.01). Stem cells could weaken the ERS-induced cell apoptosis, especially reducing the number of cells in the late stage of apoptosis from 5.4% to 1.1%. The protein level of GRP78, PERK, ATF4, TMEM119, and BMP6 in the group of ERS, ERS + stem cells, and si-PERK + ERS + stem cells were all significantly higher than those in control group, and the group of ERS + stem cells was the highest, all of the differences were significant (P < 0.01). However, the protein level of CDK4 and Cyclin D presented an absolutely opposite trend and the difference was still significant (P < 0.05). The group of si-PERK + ERS + stem cell was lower than those in the group of ERS + stem cell but higher than those in the group of ERS (P < 0.05). The level of Caspase 3 in the latter three groups was significantly higher than those in the control group, and the group of ERS was the highest (P < 0.01). Besides, the relative level of Bcl-2/Bax in control group was 1, but the group of ERS was about 0.5, and there was significant difference (P < 0.01). The ratio of Bcl-2/Bax in the group of ERS + stem cells was more than 2 and significantly higher than those of other groups. CONCLUSION: ACSCs could reduce ERS-induced chondrocyte apoptosis by PERK and Bax/Bcl-2 signaling pathway.

Increasing Level of Leisure Physical Activity Could Reduce the Risk of Hip Fracture in Older Women: A Dose-Response Meta-analysis of Prospective Cohort Studies.

We carried out the study to investigate and quantitatively assess the potential association between current level of physical activity and the risk of osteoporosis hip fracture in older women. Relevant publications before October 2015 were identified using the PubMed and Ovid searching tools. A dose-response meta-analysis was carried out to combine and analysis results. Fourteen prospective studies were included in the meta-analysis. A general analysis of 9 studies showed a significant inverse relationship between increasing level of physical activity and risk of hip fracture in older women [relative risk (RR) = 0.93, 95% confidence interval (95% CI): 0.91-0.96]. The result of a sensitivity analysis was consistent with the general analysis (RR = 0.94, 95% CI: 0.93-0.96). The association between increasing level of physical activity and risk of wrist fracture was not statistically significant in a general analysis of three studies (RR = 1.004, 95% CI: 0.98-1.03). A potential direct association between increasing level of physical activity and risk of wrist fracture was observed after removing 1 study with the greatest weight (RR = 1.01, 95% CI: 1.00-1.03). No significant publication bias was observed in our analysis. Our results show that increasing level of physical activity within an appropriate range may reduce the risk of hip fracture but not the risk of wrist fracture in older women.