Role of fibroblast growth factor receptor 1 in the bone development and skeletal diseases

Accumulating data suggest that FGFs/FGFR1 plays essential roles in the bone development and human skeletal diseases. Conditional inactivation of fgfrl caused different phenotypes displaying in different cells or specific organs and revealed some novel functions of FGFR1 in bone development. Fgfrl mutation mainly induced 2 types of human skeletal diseases, craniosynostosis syndrome and dysplasias. Similar mutation of fgfrl in mouse model just mimicked the phenotype that happened in human. These fa- cilitate the investigation on the underlying mechanism of the diseases. Here we mainly focused on the ad- vance of FGFR1 function in the bone development and its mutation caused skeletal diseases.

Osteoblastic microRNAs in skeletal diseases:Biological functions and therapeutic implications

Skeletal diseases normally represents a grievous imbalance between osteoblasts for bone formation and osteoclasts for bone resorption.A lack of osteogenic function can make it difficult to repair pathological bone erosion.Therefore,substantial efforts have been made to remedy these issues,with the aid of bioactive molecules,herbs and materials.Following recent insights,the importance of epigenetic gene regulation is increasingly evident,especially microRNAs.MicroRNAs can silence target genes by inhibiting mRNA translation or degrading mRNA molecules by binding to their 3′-untranslated region.There is accumulating evidence indicating that the miRNAs significantly involved in osteogenic gene expression,signaling pathway intervention and programmed cell death.Besides,numerous new target drugs(microRNA inhibitors or agonists)have been proposed to exploit its value in skeletal physiology and pathology.In this review,we mainly discuss the role of microRNAs in the context of skeletal disease-associated osteoblast differentiation,the applications of microRNA polymorphisms as biomarkers for diagnostic and therapeutic targets,and the challenges to meet this goal.Our summary provides novel horizon for improving the therapeutic effect of microRNAs,which may be beneficial to the further clinical translation of microRNAs in the treatments of skeletal diseases.

TGF-β and BMP signaling in osteoblast,skeletal development,and bone formation,homeostasis and disease

INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.

Effect of ACTN3 gene polymorphism on the pathogenic phenotype of related diseases and its treatment prospect

Theα-actin-3 protein expressed by ACTN3 gene cod is a troponin binding protein,which is mainly located in the Z disk on skeletal muscle fibers.Due to the homozygous nonsense polymorphism(R577X)of the gene,about 1.5 billion people in the world have lost the expression of this protein.Because the presence ofα-actin-3 protein increases skeletal muscle cells to be compliant,the gene is often referred to as the“speed gene”,and current studies suggest that this gene polymorphism has varying degrees of influence on muscle injury,decreased endurance,hypomyopathy,osteoporosis,endocrine disease,cardiovascular disease.This is a review of the current effects of ACTN3 gene polymorphisms on a variety of diseases,as well as its possible intervention treatment options.

Roles of focal adhesion proteins in skeleton and diseases

The skeletal system,which contains bones,joints,tendons,ligaments and other elements,plays a wide variety of roles in body shaping,support and movement,protection of internal organs,production of blood cells and regulation of calcium and phosphate metabolism.The prevalence of skeletal diseases and disorders,such as osteoporosis and bone fracture,osteoarthritis,rheumatoid arthritis,and intervertebral disc degeneration,increases with age,causing pain and loss of mobility and creating a huge social and economic burden globally.Focal adhesions(FAs)are macromolecular assemblies that are composed of the extracellular matrix(ECM),integrins,intracellular cytoskeleton and other proteins,including kindlin,talin,vinculin,paxillin,pinch,Src,focal adhesion kinase(FAK)and integrin-linked protein kinase(ILK)and other proteins.FA acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell–environment communications and modulates important processes,such as cell attachment,spreading,migration,differentiation and mechanotransduction,in different cells in skeletal system by impacting distinct outside-in and inside-out signaling pathways.This review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases.

Muscle mass loss and intermuscular lipid accumulation were associated with insulin resistance in patients receiving hemodialysis

Background An accelerated muscle wasting was the pivotal factor for protein-energy wasting in end stage renal disease. However, very few researches have examined the skeletal muscle quantity and quality in clinical patients. This study investigated the muscle morphologic changes by magnetic resonance imaging （MRI） and analyzed the related factors in hemodialysis patients. Methods Fifty-eight patients receiving maintenance hemodialysis （HD） were investigated and 28 healthy adults with gender and age matched were used as controls （Control）. Anthropometry, cytokine factors, and laboratory data were measured. The muscle and intermuscular adipose tissues （IMAT） were analyzed via a Thigh MRI. The bicep samples were observed after HE staining. Homeostatic model assessment of insulin resistance （HOMA-IR） was measured and their association with muscle wasting was analyzed. Results HD patients tended to have a lower protein diet, anthropometry data, and serum albumin, but the C reactive protein and interleukin-6 increased significantly. The MRI showed that HD patients had less muscle mass and a lower muscle/total ratio, but the fat/muscle and IMAT was higher when compared to the Control group. The muscle fiber showed atrophy and fat accumulation in the biceps samples come from the HD patients. Moreover, we found that the HD patients presented with a high level of plasma fasting insulin and increased HOMA-IR which negatively correlated with the muscle/ total ratio, but positively with the fat/muscle ratio. Conclusions Muscle wasting presented early before an obvious malnutrition condition emerged in HD patients. The main morphological change was muscle atrophy along with intermuscular lipid accumulation. Insulin resistance was associated with muscle wasting in dialysis patients.