A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats

Spinal cord injury（SCI）-induced bone loss represents the most severe osteoporosis with no effective treatment.Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae,and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography（m CT）, micro-finite element, histology, and serum biochemical analyses.At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.

Effects of DHRS3 in C2C12 Myoblast Differentiation and Mouse Skeletal Muscle Injury

Myoblast differentiation is an essential process during skeletal muscle development.C2C12 myoblast is a commonly used experimental model to study muscle cell differentiation in vitro.Dehydrogenase/reductase(SDR family)member 3(DHRS3)is a highly conserved member in short-chain alcohol dehydrogenase/reductase superfamily and has been shown to be involved in the metabolism of retinol.Previous experimental results showed that the expression of DHRS3 increased significantly during the differentiation of myoblasts differentiation.However,the effect of DHRS3 on mouse muscle cell differentiation was unclear.The objective of current study was to determine if DHRS3 affected muscle cell differentiation,and if DHRS3 was involved in muscle regeneration.Protein expression was determined by western blot and immunofluorescence analysis.The activation and inhibition of DHRS3 increased and decreased C2C12 myoblast differentiation respectively,which indicated that DHRS3 could affect C2C12 myoblast differentiation.DHRS3 expression was significantly changed during muscle regeneration,with the regeneration of muscle injury,the expression of DHRS3 tended to increase first and then decrease.It suggested that DHRS3 might be involved in muscle regeneration.In summary,this study confirmed the involvement of DHRS3 in C2C12 myoblast differentiation and mouse skeletal muscle regeneration and provided a theoretical basis for further elucidating the molecular mechanism of muscle development.

Myoprotective effects of bFGF on skeletal muscle injury in pressure-related deep tissue injury in rats

Background:Pressure ulcers(PUs)are a major clinical problem that constitutes a tremendous economic burden on healthcare systems.Deep tissue injury(DTI)is a unique serious type of pressure ulcer that arises in skeletal muscle tissue.DTI arises in part because skeletal muscle tissues are more susceptible than skin to external compression.Unfortunately,few effective therapies are currently available for muscle injury.Basic fibroblast growth factor(bFGF),a potent mitogen and survival factor for various cells,plays a crucial role in the regulation of muscle development and homeostasis.The main purpose of this study was to test whether local administration of bFGF could accelerate muscle regeneration in a rat DTI model.Methods:Male Sprague Dawley(SD)rats(age 12 weeks)were individually housed in plastic cages and a DTI PU model was induced according to methods described before.Animals were randomly divided into three groups:a normal group,a PU group treated with saline,and a PU group treated with bFGF(10μg/0.1 ml)subcutaneously near the wound.Results:We found that application of bFGF accelerated the rate of wound closure and promoted cell proliferation and tissue angiogenesis.In addition,compared to saline administration,bFGF treatment prevented collagen deposition,a measure of fibrosis,and up-regulated the myogenic marker proteins MyHC and myogenin,suggesting bFGF promoted injured muscle regeneration.Moreover,bFGF treatment increased levels of myogenesis-related proteins p-Akt and p-mTOR.Conclusions:Our findings show that bFGF accelerated injured skeletal muscle regeneration through activation of the PI3K/Akt/mTOR signaling pathway and suggest that administration of bFGF is a potential therapeutic strategy for the treatment of skeletal muscle injury in PUs.