Effect and mechanism of Polygonatum sibiricum polysaccharide on osteogenic differentiation of bone mesenchymal stem cells(BMSCs)

Objective:To investigate the effects and mechanisms of Polygonatum sibiricum polysaccharide(PSP)on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods:The mouse BMSCs were cultured and induced in osteoblast medium(OBM)containing finalconcentrations(0 mg/L,12.5 mg/L,25 mg/L,and 50 mg/L)of PSP.The proliferation and cytotoxicity of BMSCs were detected by MTT assay.Alkaline phosphatase(ALP)and Alizarin red S staining were performed after 7 days' ossification-inducing culture.The mRNA expressions of ALP,Runx2 and osteocalcin(OCN)were determined by fluorescence quantitative PCR(qPCR).The mRNA and protein expressions of Tafazzin(TAZ)(a key effector of Hippo pathway)were measured by qPCR and western blotting,respectively.Results:PSP was non-cytotoxicwithin the dose range of 12.5-50 mg/L and had no impact on the proliferation of BMSCs.The activity of ALP,the intensity of ALP staining,and the formation of mineralized nodules were increased by PSP treatment(25 and50 mg/L)(P<0.01).Moreover,administration of 25 mg/L PSP significantly enhanced the mRNA levels of osteoblastic differentiation makers ALP,Runx2 and OCN as well as the mRNA and protein expressions of TAZ(P<0.01).Conclusion:PSP could promote osteogenic differentiation of BMSCs,and the mechanisms might be related to the activation of TAZ in the Hippo signaling pathway.

Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17^(+) γδ T cells

Spinal cord injury(SCI)causes motor,sensory,and autonomic dysfunctions.The gut microbiome has an important role in SCI,while short-chain fatty acids(SCFAs)are one of the main bioactive mediators of microbiota.In the present study,we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI.Allen’s method was utilized to establish an SCI model in Sprague-Dawley(SD)rats.The animals received water containing a mixture of 150 mmol/L SCFAs after SCI.After 21 d of treatment,the Basso,Beattie,and Bresnahan(BBB)score increased,the regularity index improved,and the base of support(BOS)value declined.Spinal cord tissue inflammatory infiltration was alleviated,the spinal cord necrosis cavity was reduced,and the numbers of motor neurons and Nissl bodies were elevated.Enzyme-linked immunosorbent assay(ELISA),real-time quantitative polymerase chain reaction(qPCR),and immunohistochemistry assay revealed that the expression of interleukin(IL)-10 increased and that of IL-17 decreased in the spinal cord.SCFAs promoted gut homeostasis,induced intestinal T cells to shift toward an anti-inflammatory phenotype,and promoted regulatory T(Treg)cells to secrete IL-10,affecting Treg cells and IL-17^(+)γδT cells in the spinal cord.Furthermore,we observed that Treg cells migrated from the gut to the spinal cord region after SCI.The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17^(+)γδT cells in the spinal cord,which inhibits the inflammatory response and promotes the motor function in SCI rats.Our findings suggest that there is a relationship among gut,spinal cord,and immune cells,and the“gut-spinal cord-immune”axis may be one of the mechanisms regulating neural repair after SCI.

Changes in the gut microbiota of osteoporosis patients based on 16S rRNA gene sequencing:a systematic review and meta-analysis

Background:Osteoporosis(OP)has become a major public health issue,threatening the bone health of middle-aged and elderly people from all around the world.Changes in the gut microbiota(GM)are correlated with the maintenance of bone mass and bone quality.However,research results in this field remain highly controversial,and no systematic review or meta-analysis of the relationship between GM and OP has been conducted.This paper addresses this shortcoming,focusing on the difference in the GM abundance between OP patients and healthy controls based on previous 16S ribosomal RNA(rRNA)gene sequencing results,in order to provide new clinical reference information for future customized prevention and treatment options of OP.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA),we comprehensively searched the databases of Pub Med,Web of Science,Embase,Cochrane Library,and China National Knowledge Infrastructure(CNKI).In addition,we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis.We also implemented the Newcastle-Ottawa Scale(NOS),funnel plot analysis,sensitivity analysis,Egger’s test,and Begg’s test to assess the risk of bias.Results:This research ultimately considered 12 studies,which included the fecal GM data of 2033 people(604 with OP and 1429 healthy controls).In the included research papers,it was observed that the relative abundance of Lactobacillus and Ruminococcus increased in the OP group,while the relative abundance for Bacteroides of Bacteroidetes increased(except for Ireland).Meanwhile,Firmicutes,Blautia,Alistipes,Megamonas,and Anaerostipes showed reduced relative abundance in Chinese studies.In the linear discriminant analysis Effect Size(LEfSe)analysis,certain bacteria showed statistically significant results consistently across different studies.Conclusions:This observational meta-analysis revealed that changes in the GM were correlated with OP,and variations in some advantageous GM might involve regional differences.