Osteoporosis significantly impacts the normal life of the elderly and is reported to be closely related to dysfunction of osteoblastic differentiation. Runt-related transcription factor-2 (Runx2) is a critical transcriptional factor involved in the regulation of osteoblast differentiation. Omarigliptin is a novel dipeptidyl peptidase-4 (DDP-4) inhibitor and this study proposes to probe into its possible therapeutic function against Osteoporosis by investigating its impacts on osteoblastic differentiation. Osteogenic medium was used to induce osteoblastic differentiation in MC3T3‑E1 cells, and was verified by the increased alkaline phosphatase (ALP) activity, enhanced mineralization, and promoted expression level of osteoblastic differentiation-related factors, including bone morphogenetic protein-2 (BMP-2), ALP, osteocalcin (Ocn), collagen type I alpha 1 (Col1a1), Collagen Type I alpha 2 (Col1a2), Runx2, osterix (Sp7), fibroblast growth factor receptor 2 (Fgfr2), and fibroblast growth factor receptor 3 (Fgfr3), accompanied by the activation of the p38 and Akt pathways. After treatment with Omarigliptin, the ALP activity and mineralization were further promoted, accompanied by the further upregulation of osteoblastic differentiation-related factors, and activation of the p38 and Akt pathways. Lastly, Omarigliptin-induced osteoblastic differentiation, promoted ALP activity, and increased expression levels of Sp7, Fgfr2, Fgfr3, BMP-2, Ocn, ALP, Col1a1, and Col1a2, in the osteogenic medium- cultured MC3T3‑E1 cells were dramatically abolished by the knockdown of Runx2. Taken together, our data reveal that Omarigliptin promoted osteoblastic differentiation by regulating Runx2.
Background The contribution of Cutibacterium acnes (C. acnes) infection to intervertebral disc degeneration (IDD) and the antibiotic therapy has evoked several controversies in recent years. While some microbiology studies report bacterial disc infection within IDD patients, others attribute the positive results to contamination during prolonged cultures. In addition to the clinical controversy, little was known about the mechanism of C. acnes-caused Modic changes (MCs) if C. acnes was the pathogenic factor. Objectives This study aimed to investigate the inflammatory mechanism of MCs induced by different phylotypes of C. acnes in patients with IDD. Methods Specimens from sixty patients undergoing microdiscectomy for disc herniation were included, C. acnes were identified by anaerobic culture, followed by biochemical and PCR-based methods. The identified species of C. acnes were respectively inoculated into the intervertebral discs of rabbits. MRI and histological change were observed. Additionally, we detected MMP expression in the rabbit model using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results Of the 60 cases, 18 (30%) specimens were positive for C. acnes, and we identified 4 of 6 defined phylogroups: IA, IB, II and III. The rabbits that received Type IB or II strains of C. acnes showed significantly decreased T1WI and higher T2WI at eighth weeks, while strain III C. acnes resulted in hypointense signals on both T1WI and T2WI. Histological examination results showed that all of the three types of C. acnes could cause disc degeneration and endplates rupture. Moreover, endplate degeneration induced by type IB or II strains of C. acnes is related with MMP13 expression. Meanwhile, strain III C. acnes might upregulated the level of MMP3. Conclusion This study suggested that C. acnes is widespread in herniated disc tissues. Different types of C. acnes could induce different MCs by increasing MMP expression.
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