HNGF6A Inhibits Oxidative Stress-Induced MC3T3-E1 Cell Apoptosis and Osteoblast Phenotype Inhibition by Targeting Circ_0001843/miR-214 Pathway.
Zhu. Xiao X; Zhao. Ziping Z; Zeng. Canjun C; Chen. Bo B; Huang. Haifeng H; Chen. Youming Y; Zhou. Quan Q; Yang. Li L; Lv. Jicheng J; Zhang. Jing J; Pan. Daoyan D; Shen. Jie J; Duque. Gustavo G; Cai. Daozhang D
Key Findings
- HNGF6A reduced oxidative stress‑induced death of osteoblasts in vitro
- It boosted expression of bone‑formation proteins and mineralization
- The effect involved lowering circ_0001843, raising miR‑214, and dampening p38/JNK signaling
Practical Outcomes
- While the results are promising for bone health, they are limited to cell‑culture data. Biohackers should view this as early evidence that humanin analogs could support bone metabolism, but no human dosage or safety data exist yet. Until clinical studies appear, focus on proven bone‑support strategies (adequate calcium, vitamin D, resistance training) and treat humanin supplements as experimental.
Summary
A lab study found that a humanin‑like peptide called HNGF6A can protect bone‑forming cells from oxidative damage and help them keep their bone‑building activity, working through a specific RNA signaling pathway. The work was done in mouse cells, not people, so it’s not a ready‑to‑use protocol but hints that humanin‑based compounds might aid bone health.
Abstract
Humanin (HN), a mitochondrial derived peptide, plays cyto-protective role under various stress. In this study, we aimed to investigate the effects of HNGF6A, an analogue of HN, on osteoblast apoptosis and differentiation and the underlying mechanisms. Cell proliferation of murine osteoblastic cell line MC3TC-E1 was examined by CCK8 assay and Edu staining. Cell apoptosis was detected by Annexin V assay under H<sub>2</sub>O<sub>2</sub> treatment. The differentiation of osteoblast was determined by Alizarin red S staining. We also tested the expression of osteoblast phenotype related protein by real-time PCR and Western blot. The interaction between Circ_0001843 and miR-214, miR-214 and TAFA5 was examined by luciferase report assay. Circ_0001843 was inhibited by siRNA and miR-214 was suppressed by miR-214 inhibitor to determine the effects of Circ_0001843 and miR-214 on cell proliferation, apoptosis, and differentiation. HNGF6A, an analogue of HN, exerted cyto-protection and osteogenesis-promotion in MC3T3-E1 cells. The expression of osteoblast phenotype related protein was significantly induced by HNGF6A. Additionally, HNGF6A treatment decreased Circ_0001843 and increased miR-214 levels, as well as inhibited the phosphorylation of p38 and JNK. We further found that Circ_0001843 directly bound with miR-214, which in turn inhibited the phosphorylation of p38 and JNK. Furthermore, both Circ_0001843 overexpression and miR-214 knockdown significantly decreased the cyto-protection and osteogenic promotion of HNGF6A. In summary, our data showed that HNGF6A protected osteoblasts from oxidative stress-induced apoptosis and osteoblast phenotype inhibition by targeting Circ_0001843/miR-214 pathway and the downstream kinases, p38 and JNK.
Study Information
pubmed
2020
2020-03-18T00:00:00.000Z
10.1007/s00223-020-00660-z
20
49