Object: Primary osteoporosis (PO) is the most common bone disease, which is characterized by decreased bone mass, damage of bone tissue microstructure, increased bone fragility and prone to fracture. Gut microbiome may be involved in bone metabolism of PO through gut–brain axis regulation of immune system and endocrine system, however, the specific mechanism is still unclear. The purpose of this study was to characterize the gut microbiome of patients with PO and its possible role in the occurrence and development of the disease. Methods: Fecal samples were collected from 48 PO patients and 48 healthy controls (HC). The composition of gut microbiome community was analyzed by 16s rDNA amplification sequencing, and the difference of gut microbiome composition between PO patients and HC individuals was compared. PICRUSt was also used to predict the biological function of gut microbiome in patients with PO, and to explore its possible role in the occurrence and development of this disease. The classification model is constructed by random forest algorithm so as to screen the key biomarkers. Result:The diversity of gut microorganisms in PO patients was significantly higher than that in HC group (p<0. 05) and there was significant difference in microbial composition in PO group. The abundance of Dialister (0.036 vs. 0.004, p<0.001) and Faecalibacterium (0.331 vs. 0.132, p<0.001) were significantly enriched which were the key flora related to PO. Although no significant correlation between bone mineral density and the richness of microbial communities is found, PICRUST results show that there are a wide range of potential pathways between gut microbiome and PO patients, including genetic information processing, metabolism, environmental information processing, cellular processes, human diseases and organic systems. Notably, the discriminant model based on dominant microflora can effectively distinguish PO from HC (AUC=93.56). Conclusions: The findings show that PO is related to the change of gut microbiome, especially the enriched Dialister and Faecalibacterium genera, which give new clues to understand the disease and provide markers for the diagnosis and new strategies for intervention treatment of the disease.

Osteoarthritis (OA) is a multifactorial joint disease characterized by degeneration of articular cartilage, which leads to joints pain, disability and reduced quality of life in patients with OA. Interpreting the potential mechanisms underlying OA pathogenesis is crucial to the development of new disease modifying treatments. Although multiple factors contribute to the initiation and progression of OA, gut microbiota has gradually been regarded as an important pathogenic factor in the development of OA. Gut microbiota can be regarded as a multifunctional “organ”, closely related to a series of immune, metabolic and neurological functions. This review summarized research evidences supporting the correlation between gut microbiota and OA, and interpreted the potential mechanisms underlying the correlation from four aspects: immune system, metabolism, gut-brain axis and gut microbiota modulation. Future research should focus on whether there are specific gut microbiota composition or even specific pathogens and the corresponding signaling pathways that contribute to the initiation and progression of OA, and validate the potential of targeting gut microbiota for the treatment of patients with OA.

MicroRNAs (miRNAs) as small non-coding RNAs act as either tumor suppressors or oncogenes in human cancers, of which miR-149-5p (miR-149) is involved in tumor growth and metastasis, but its role and molecular mechanisms underlying osteosarcoma growth are poorly understood. The correlation of miR-149 expression with clinicopathological characteristics and prognosis in patients with sarcoma was analyzed by The Cancer Genome Atlas (TCGA) RNA-sequencing data. Osteosarcoma cell growth affected by miR-149 was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. As a result, we found that the expression level of miR-149 was markedly downregulated in human sarcoma samples and were negatively associated with tumor size, acting as an independent prognostic factor for overall survival of the sarcoma patients. Restoration of miR-149 expression suppressed osteosarcoma cell growth, while its knockdown reversed these effects. Furthermore, we identified TNFRSF12A (TNF receptor superfamily member 12A), also called fibroblast growth factor–inducible 14 (Fn14) as a direct target of miR-149, and TNFRSF12A and its ligand TNFSF12 (TNF superfamily member 12), also called tumor necrosis factor–related weak inducer of apoptosis (TWEAK), were both negatively correlated with miR-149 expression in sarcoma samples. Knockdown of TNFRSF12A suppressed cell growth, but its overexpression weakened the antiproliferative effects of miR-149 via the PI3K/AKT (AKT serine/threonine kinase) signaling pathway. Altogether, our findings show that miR-149 functions as a tumor suppressor in osteosarcoma via inhibition of the TWEAK–Fn14 axis and represents a potential therapeutic target in patients with osteosarcoma.

Intestinal flora located within the intestinal tract comprises a large number of cells, which are referred to as the second gene pool of the human body and form a complex symbiotic relationship with the host. The knowledge of the complex interaction between the intestinal flora and various life activities of the host is a novel and rapidly expanding field. Recently, many studies are being conducted on the relationship between the intestinal flora and bone homeostasis and indicate that the intestinal flora can regulate bone homeostasis via the host immune, metabolic, and endocrine systems. What’s more, based on several clinical and preclinical pieces of evidence, changing the composition and function of the host intestinal flora through the application of probiotics, prebiotics, and fecal microbiota transplantation is being considered to be a potential novel target for the regulation of bone homeostasis. Here, we searched relevant literature and reviewed the role of the intestinal flora in the regulation of bone homeostasis and its modulating interventions.

Background/Aim: Secreted phosphoprotein 24 kD (spp24) has been shown to inhibit bone morphogenetic protein 2 (BMP2)-induced cancer growth in several tumor models. In this study, we aimed to investigate the effects spp24 on the growth of prostate cancer caused by BMP2 in vitro and in vivo. Materials and Methods: The effects of BMP2 and spp24 on PC-3 cell viability were analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. A subcutaneous tumor model and intratibial tumor model was established using PC-3 cells. Tumor growth was assessed through gross examination and radiography during the experiment. Then, after sacrifice, tumor cell apoptosis and tumor cell proliferation were assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and immunochemical analysis. Results: BMP2 stimulated the PC-3 cell proliferation in vitro and spp24 could abolish the effect of BMP2. In a xeneograft tumor model, BMP2 promoted the subcutaneous and intratibial tumor growth, while spp24 dramatically inhibited the tumor growth induced by BMP2. Histological examination showed that spp24 also abolished the BMP2-induced proliferating cell nuclear antigen (PCNA) expression and promoted tumor cell apoptosis. Conclusion: Spp24 can inhibit the growth of prostate cancer and its bone metastasis induced by BMP2; spp24 may have great potential to be a therapeutic agent in clinical situations.