ObjectiveTo investigate the role and mechanism of ribosomal DNA （rDNA） transcription and ribosome biogenesis in muscle atrophy induced by acute kidney injury （AKI）. MethodsEight male C57BL/6 mice were randomly divided into a control group （Ctrl） and a model group （AKI）. An AKI model was established via intraperitoneal injection of cisplatin. Muscle atrophy was phenotypically assessed by measuring muscle mass， myofiber cross-sectional area （HE staining）， and mRNA expression levels of atrophy-related genes （Murf-1， Atrogin-1， Igf-1） using qRT-PCR. In vivo protein synthesis rates were determined via the SUnSET assay （puromycin incorporation）. Ribosome biogenesis was evaluated by assessing rRNA content and 47S pre-rRNA expression levels. Myotubes differentiated from mouse skeletal muscle cell lines （C2C12 myotubes） were treated with serum from AKI mice， and the effects on rDNA transcription， ribosome biogenesis， and protein metabolism were analyzed using chromatin immunoprecipitation followed by quantitative polymerase chain reaction （ChIP-qPCR） and Western blot. ResultsAKI successfully induced muscle atrophy， as evidenced by a significant reduction in skeletal muscle mass. The most pronounced decrease occurred in the extensor digitorum longus muscle （21.0%， P 0.01）， along with a trend toward reduced myofiber cross-sectional area. At the molecular level， AKI inhibited muscle protein synthesis （83.14% reduction in puromycin incorporation， P 0.000 1） and impaired ribosome biogenesis， manifested by suppressed rDNA transcription elongation （52.62% decrease in 47S pre-rRNA ITS-1 levels， P 0.01） and reduced total rRNA content （65.29%， P 0.000 1）. In contrast， serum from AKI mice promoted rDNA transcription initiation and protein synthesis in C2C12 myotubes in vitro. ConclusionAKI induces muscle atrophy by suppressing rDNA transcription and ribosome biogenesis in skeletal muscle， leading to impaired protein synthesis. Dysregulated ribosome biogenesis may play a critical role in AKI-induced muscle atrophy.

BACKGROUND: Based on the multi-directional differentiation potential,the combined application of proper biological materials and growth factor can repair tissue defect.OBJECTIVE: To observe the growth characteristics of rabbit bone marrow-derived mesenchymal stem cells and their osteogenic potential under the induced condition.DESIGN: A single sample experiment.SETTING: The Department of Histology and Embryology of Youjiang Medical College for Nationalities; the Affiliated Hospital of Youjiang Medical College for Nationalities.MATERIALS: This experiment was conducted at the Department of Histology and Embryology of Youjiang Medical College for Nationalities in June 2004. Male new Zealand rabbits, with a body mass of 2.0 to 2.5 kg,were provided.METHODS: Rabbit bone marrow tissue was extracted. After gradient centrifugation, adherent cells were kept for cell passage. Culture medium was used for inducing culture of osteoblast when the passage was stable (50 mL/L of Dulbecco modified culture medium of bovine serum containing 10 mmol/L of β-sodium glycerophosphate, 10 nmol/L of dexamethasone, 50 mg/L of vitamine C). The culture medium was changed every other day. Osteogenic characteristics of the bone marrow-derived mensenchymal stem cells were observed under an inverted microscope after alkaline phosphatase immunohistological staining, osteonectin and osteopontin immunocytochemical staining.MAIN OUTCOME MEASURES: ① Morphological observation of bone marrow-derived mesenchymal stem cells; ② Osteogenic characteristics of bone marrow-derived mesenchymal stem cells.RESULTS: ① Morphological observation of bone marrow-derived mensenchymal stem cells: Primary rabbit bone marrow-derived mesenchymal stem cells could cover the Petri dish fully in 7 or8 days and could passage stably. Generative cells began to passage in 5 or 6 days. ② Osteogenic characteristics of bone marrow-derived mensenchymal stem cells:Alkaline phosphatase immunohistochemical staining showed a lot of brown particles in the kytoplasm, but no colored cells were found in the control group. Osteonectin and osteopontin immunohistochemical detection found that the nucleus was light blue and a lot of brown particles appeared in the kytoplasm, presenting obvious strong positive, but no brown particles appeared in the control group.CONCLUSION: After combined induced culture with dexamethasone, vitamine C and β-sodiumglycerophosphate, rabbit bone marrow mensenchymal stem cells showed the morphological and biological characteristics of osteoblasts with osteoblastic activity, and were able to supply autologous seed cells for constructing in vitro tissue engineered bone in a short period of time.