With increasing age, the microenvironment in the bone marrow is altered, leading to a decrease in bone marrow mesenchymal stem cell (BMSC) differentiation, which reduces the number of bone cells and weakens osteogenic capacity, resulting in osteoporosis (OP). The clinical manifestations of OP include bone loss, bone microstructural destruction and altered bone quality. Bone morphogenetic protein 2 (BMP2) serves an important role in inducing the osteogenic differentiation of mesenchymal stem cells (MSCs). Regulating the bone marrow matrix microenvironment and promoting osteogenic differentiation of BMSCs is of significance for both the prevention and treatment of OP. In the present study, isobaric tags for relative and absolute quantification (iTRAQ) high-throughput proteomics technology was combined with bioinformatics analysis to screen 249 differentially expressed proteins in human MSCs overexpressing BMP2, of which 173 were upregulated and 76 proteins were downregulated. The proteins were also involved in signaling pathways associated with extracellular matrix organization, osteoblast differentiation, ossification, bone development, chondrocyte differentiation and bone morphogenesis. By carefully screening the proteins, N-cadherin (CDH2), a protein with osteogenic differentiation potential, was verified by perturbations in the background of BMP2 overexpression. The role of CDH3 in the osteogenic differentiation of MSCs was confirmed by the regulation of several cognate osteogenic markers, suggesting CDH2 as a promising candidate in the field of osteogenesis.
Background: Recruitment of gene modify bone marrow mesenchymal stem cells (BMSCs) has been considered an alternative to single cell injection in articular cartilage repair. Purpose: The aim of this study was to investigate the effect whether of runt-related transcription factor 2(Runx2) overexpression bone marrow mesenchymal stem cells in vivo could improve the quality of repaired tissue of a knee cartilage defect in a rabbit model. Methods: Thirty-two New Zealand rabbits were randomly divided into four groups.The blank group (Con) don’t received anything, the model group (Mo) was administered saline, the simple stem cell group (MSCs) received MSCs injection, the Runx2 transfection group (R-MSCs) received Runx2 overexpression MSCs injection. After adapting to the environment for a week, a 5 mm diameter cylindrical osteochondral defect was created in the center of medial femoral condyle. Cell and saline injections are performed in the first and third weeks after surgery. The cartilage repair was evaluated by macroscopically and microscopically at 4 and 8 weeks. Results: Macroscopically, defects were filled and surfaces were smoother in the MSCs groups than in the Mo group at 4 weeks. Microscopically, the R-MSCs group showed coloration similar to surrounding normal articular cartilage tissue at 8weeks in masson trichrome staining. The COL-Ⅱ, SOX9 and Aggrecan mRNA expression of MSCs was enhanced at 4 weeks compared with R-MSCs, then the expression reduced at 8 weeks, but was still higher than Mo group level (P<0.05). The western blot examination revealed that the COL-Ⅱand SOX9 expression of MSCs was higher than R-MSCs at 4 weeks, then the expression reduced at 8 weeks, but was still higher than Mo level (P<0.05). The IL-1β content in joint fluid also revealed that cartilage repair with R-MSCs was better than that with MSCs at 8 weeks (P<0.05). Conclusions: The R-MSCs group showed cellular morphology and arrangement similar to surrounding normal articular cartilage tissue, Runx2 overexpression of MSCs resulted in overall superior cartilage repair as compared with MSCs at 8 weeks.
BackgroundAvascular necrosis of femoral head(ANFH)is a common disease in orthopedics, which seriously affects the quality of life of patients. At present, there is no clear method to solve it in clinical practice. In order to cope with this worldwide problem, many scholars have devoted themselves to the research on the treatment of ANFH. Promoting the osteogenic differentiation and directed migration of stem cells is one of the main ideas for the treatment of ANFH. In recent years, more and more researches have begun to pay attention to Chinese medicine and Chinese medicine extracts. At present, in the field of bone regeneration, epimedium is the most in-depth study of Chinese herbal medicine, and Icariin is one of the main active ingredients of epimedium. MethodsDifferent concentrations of Icariin were applied to bone marrow mesenchymal stem cells (BMSCs), and the optimal concentration of Icariin to promote osteogenic differentiation and migration of BMSCs was observed. Then the exosomes from osteoblasts were combined with the optimal concentration of Icariin to BMSCs, observe the effect of promoting osteogenic differentiation and migration of BMSCs. Using high-throughput sequencing, analyze the composition of osteoblast-derived exosomes, predict the target miRNA, and then use miRNA minic and inhibitor to verify. ResultsThe optimal concentration of Icariin to promote osteogenic differentiation and migration of BMSCs is 1×10-7 M. Icariin combined with osteoblast-derived exosomes can effectively promote the osteogenic differentiation and migration of BMSCs. The top four miRNAs which content in osteoblast-derived exosomes are let-7a-5p, miR-100-5p, miR-21-5p, miR-122-5p, and analysis shows that miR-122-5p is related to osteogenic differentiation , The verification found that miR-122-5p can significantly promote the osteogenic differentiation and migration of BMSCs. ConclusionsIcariin can clearly promote the osteogenic differentiation and migration of BMSCs, and osteoblast-derived exosomes can also effectively promote the osteogenic differentiation and migration of BMSCs, the combination of Icariin and osteoblast-derived exosomes can enhance this effect. In this process, one of its targets is miR-122-5p.
Objectives. Osteoarthritis is the leading disease of joints worldwide. Osteoarthritis may be treated by exosomes derived from Runx2-overexpressed bone marrow mesenchymal stem cells (R-BMSCs-Exos). R-BMSCs-Exos would promote the proliferation, migration, and phenotypic maintenance of articular chondrocytes. Methods. BMSCs were transfected with and without Runx2. Exosomes derived from BMSCs and R-BMSCs (BMSCs-Exos and R-BMSCs-Exos) were isolated and identified. Proliferation, migration, and phenotypic maintenance were determined in vitro and compared between groups. The mechanism for activation of Yes-associated protein (YAP) was investigated using small interfering RNA (siRNA). The exosomes’ preventive role was determined in vivo using Masson trichrome and immunohistochemical staining. Results. R-BMSCs-Exos enhance the proliferation, migration, and phenotypic maintenance of articular chondrocytes based on the YAP being activated. R-BMSCs-Exos prevent knee osteoarthritis as studied in vivo through a rabbit model. Conclusions. Findings emphasize the efficacy of R-BMSCs-Exos in preventing osteoarthritis. Potential source of exosomes is sorted out for the advantages and shortcomings. The exosomes are then modified based on the molecular mechanisms to address their limitations. Such exosomes derived from modified cells have the role in future therapeutics.
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