Muscle disuse as hindlimb unloading in early postnatal mice negatively impacts grip strength in adult mice: a pilot study.

Physical inactivity has many detrimental effects on health, yet the impact of physical inactivity in early life on muscle health in adulthood remains unknown. Early postnatal malnutrition has prolonged effects into adulthood and we propose that early postnatal (P) physical inactivity would have similar negative effects. To test this hypothesis, we exposed postnatal mice (∼P28, C57BL/6J) to 14 days of physical inactivity (shortly after weaning, from ∼P28 to P42 days of age) in the form of muscle disuse with hindlimb unloading (HU). After this early-life physical inactivity, they were allowed to normally ambulate until 5 mo of age (P140, adulthood) when they underwent 14 days of HU with and without 7-day recovery. They were then tested for physical function (grip strength) and muscles were extracted and weighed. Immunofluorescence was carried out on these muscle cross sections for analysis of myofiber cross-sectional area (fCSA), macrophage density (CD68+ cells), and extracellular matrix (ECM) area. Muscle weights and fCSA and myofiber diameter were used to quantify changes in muscle and fiber size. Compared with age-matched controls, no notable effects of early-life physical inactivity (HU) on skeletal muscle and myofiber size were observed. However, a significant reduction in adult grip strength was observed in those exposed to HU early in life. This was associated with reduced muscle macrophages and increased ECM area. Exposure to a short period of early life disuse has negative enduring effects into adulthood impacting grip strength, muscle macrophages, and muscle composition as low muscle quality.NEW & NOTEWORTHY We demonstrate that early life disuse resulted in less grip strength in adulthood. Analysis of muscle composition demonstrated no loss of whole muscle or myofiber size indicating lower muscle quality akin to premature aging. This poor muscle quality was characterized by altered muscle macrophages and extracellular matrix area. We demonstrate intriguing correlations between this loss of grip strength and muscle macrophages and also area of noncontractile tissue in the muscle.

Altered human alveolar bone gene expression in type 2 diabetes-A cross-sectional study.

OBJECTIVE: The objective of this cross-sectional study is to investigate alveolar bone gene expression in health and diabetes through ribonucleic acid (RNA) sequencing and bioinformatics analysis. BACKGROUND: It is relatively unknown how type 2 diabetes modulates gene expression in alveolar bone in humans. Clinical concern regarding increased implant failure rate in patients with diabetes has been discussed in the literature. Previous studies in animal models and humans have suggested an imbalance between the genes regulating bone formation with data suggesting bone resorption in diabetes. However, there is lack of data regarding a comprehensive gene expression from human alveolar bone in diabetes. METHODS: Alveolar bone was collected from healthy and type 2 diabetic subjects undergoing periodontal and implant surgeries. The homogenized RNA sample was then extracted and analyzed for quantity and quality. RNA samples were further purified using ribosomal RNA depletion technique and processed for RNA sequencing and analysis. Expression levels for mRNAs were performed by calculating FPKM ([total_exon_fragments/mapped reads (millions) × exon length (kB)]), and differentially expressed mRNAs were selected with log2 (fold change) >1 or log2 (fold change) ≤1 and with a parametric F test comparing nested linear models. RESULTS: Eighteen bone samples (10 healthy, 8 patients with diabetes) were analyzed for gene expression. The mean age and HbA1c% of healthy versus diabetic subjects were as follows: age (55.3 ± 17.5 vs 63.9 ± 8.7 years) and HbA1c% (5.6 ± 0.29 vs 7.3 ± 2.4), respectively. Sequencing analysis showed that expression of genes that regulate bone turnover like TGFB1, LTBP4, IGF1, BMP2, BMP4, BMP6, SMAD1, RUNX2, MCSF, and THRA was significantly downregulated in diabetes samples compared with healthy controls with overall reduced expression of genes in the bone regulation pathway in patients with diabetes. Bioinformatics analysis for the altered genes highlighted several pathways related to bone homeostasis and inflammation in diabetes. Periodontitis did not affect the gene expression pattern based on diabetes status. CONCLUSIONS: Altered expression of genes due to downregulation of certain pathways that are involved in bone turnover and inflammation suggests that overall wound healing and bone homeostasis may be compromised in type 2 diabetes.