Bone marrow mesenchymal stem cells (BMSCs), which were first discovered in bone marrow, are capable of differentiating into osteoblasts, chondrocytes, fat cells, and even myoblasts, and are considered multipotent cells. As a result of their potential for multipotential differentiation, self-renewal, immune regulation, and other effects, BMSCs have become an important source of seed cells for gene therapy, tissue engineering, cell replacement therapy, and regenerative medicine. MicroRNA (miRNA) is a highly conserved type of endogenous non-protein-encoding RNA of about 19–25 nucleotides in length, whose transcription process is independent of other genes. Generally, miRNA plays roles in regulating cell proliferation, differentiation, apoptosis, and development by binding to the 3′ untranslated region of target mRNAs, whereby they can degrade or induce translational silencing. Although miRNAs play a regulatory role in various metabolic processes, they are not translated into proteins. Several studies have shown that miRNAs play an important role in the osteogenic differentiation of BMSCs. Herein, we describe in-depth studies of roles for miRNAs during the osteogenic differentiation of BMSCs, as they provide new theoretical and experimental rationales for bone tissue engineering and clinical treatment.

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Multiple myeloma (MM) is the most common cause of death from hematological malignancy worldwide, and recent studies have revealed that let-7b-5p can play an inhibitory role in tumorigenesis. However, the role of let-7b-5p in MM still remains unclear. The aim of this study was to elucidate the molecular mechanisms by which let-7b-5p acts as a tumor suppressor in MM. Here, quantitative real-time polymerase chain reaction results showed that the expression of let-7b-5p was remarkably reduced in MM tissues and MM cell lines (RPMI-8226 and U266 cells). Furthermore, over-expression of let-7b-5p significantly suppressed RPMI-8226 cell proliferation and induced S/G2 cell cycle arrest and apoptosis. Luciferase reporter assay results demonstrated that insulin-like growth factor receptor 1 (IGF1R) was negatively regulated by let-7b-5p at the post-transcriptional level. The mRNA and protein levels of IGF1R in RPMI-8226 cells were down-regulated by let-7b-5p. Furthermore, the cell phenotype altered by let-7b-5p inhibitor can be rescued by IGF1R silencing (si-IGF1R). Taken together, our results demonstrated that let-7b-5p functions as a tumor suppressor in MM, suggesting that let-7b-5p may be a potential therapeutic target for MM.

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Genetic polymorphisms in drug metabolism and transport genes can influence the pharmacokinetics and pharmacodynamics of chemotherapy drugs. We investigated the role of genes involved in metabolic and transport pathways in response to chemotherapy and clinical outcome of osteosarcoma patients. The association between the eight polymorphisms with response to chemotherapy and clinical outcome of patients was carried out by unconditional logistic regression analysis and Cox proportional hazard models. Of 186 patients, 98 patients showed good response to chemotherapy, 64 died, and 97 showed progression at the end of the study. Patients carrying ABCB1 rs1128503 TT genotype and T allele were more likely to have a good response to chemotherapy. ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were associated with poor response to chemotherapy. In the Cox proportional hazards model, after adjusting for potential confounding factors, patients carrying ABCB1 rs1128503 TT genotype and T allele were associated with lower risk of progression-free survival (PFS) and overall survival (OS). ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were correlated with high risk of PFS and OS. The ABCB1 TT and GSTP1 GG genotypes were significantly associated with a shorter OS. In conclusion, variants of ABCB1 rs128503, ABCC3 rs4148416, and GSTP1 rs1695 are associated with response to chemotherapy and PFS and OS of osteosarcoma patients; these gene polymorphisms could help in the design of individualized therapy.

The functional roles and clinical significances of miR-590-3p in ICC remain unclear. In the current study, we investigated the expression of miR-590-3p in tissues and sera of ICC by real-time quantitative polymerase chain reaction. We found miR-590-3p was significantly down-regulated in the sera and tissues of ICC patients, especially in those patients with lymph node metastasis or distant metastasis. AUC curves and Cox proportional hazards mode revealed serum miR-590-3p could be novel diagnostic and prognostic biomarker for ICC patients. MiR-590-3p dramatically suppressed epithelial-mesenchymal transition, cell migration, and invasion of ICC cells. SIP1 was identified as direct and functional target of miR-590-3p in ICC cells by luciferase assays. Finally, we found SIP1 expression was inversely correlated with miR-590-3p and closely related to diminished survival in ICC patients. These findings reveal functional and mechanistic roles of miR-590-3p and EMT activator SIP1 in the pathogenesis of ICC.

Fibroblast growth factor (FGF) family members are important regulators of cell growth, proliferation, differentiation, and regeneration. The abnormal expression of certain FGF family members can cause skeletal diseases, including achondroplasia, craniosynostosis syndrome, osteoarthritis, and Kashin-Beck disease. Accumulating evidence shows that FGFs play a crucial role in the growth and proliferation of bone and in the pathogenesis of certain bone-related diseases. Here, we review the involvement of FGFs in bone-related processes and diseases; FGF1 in the differentiation of human bone marrow mesenchymal stem cells and fracture repair; FGF2, FGF9, and FGF18 in osteoarthritis; FGF6 in bone and muscle injury; FGF8 in osteoarthritis and Kashin-Beck disease; and FGF21 and FGF23 on bone regulation. These findings indicate that FGFs are targets for novel therapeutic interventions for bone-related diseases. K E Y W O R D S abnormal expression, bone-related diseases, fibroblast growth factor, targeted therapy | 1741 WANG et Al.a variety of skeletal abnormalities, including achondroplasia and craniosynostosis syndrome (Kan et al., 2002). Therefore, the role of FGFs in bone-related diseases has received considerable attention. In this review, we discuss the emerging roles of fibroblast growth factors in bone-related diseases and we provide new insights into the development of novel therapies for bone-related diseases.

Bone Marrow Mesenchymal Stem Cells (BMSCs) are one of the primary cells found in the bone marrow, and they can differentiate into osteoblasts, chondrocytes, adipocytes and even myoblasts, and are, therefore, considered pluripotent cells. Because of their multipotential differentiation, selfrenewal capability, immunomodulation and other potential activities, BMSCs have become an important source of seed cells for gene therapy, tissue engineering, cell replacement therapy and regenerative medicine. Long non-coding RNA (lncRNA) is an RNA molecule greater than 200 nucleotides in length that is expressed in a variety of species, including animals, plants, yeast, prokaryotes, and viruses, but lacks an apparent open reading frame, and does not have the function of translation into proteins. Many studies have shown that lncRNAs play an important role in the osteogenic differentiation of BMSCs. Here, we describe the role of lncRNAs in the osteogenic differentiation of BMSCs, in order to provide a new theoretical and experimental basis for bone tissue engineering and clinical treatment.