1,25-Dihydroxyvitamin D deficiency induces sarcopenia by inducing skeletal muscle cell senescence.

To determine if 1,25(OH)D deficiency can induce age-related sarcopenia, the skeletal muscular phenotype of male wild-type (WT) and Cyp27b1 knockout (KO) mice were compared at 3 and 6 months of age. We found that muscle mass, grip strength and muscle fiber size were significantly decreased in aging Cyp27b1 KO male mice. The expression levels of genes related to mitochondrial metabolic activity, and antioxidant enzymes including SOD1, catalase, Nqo1 and Gcs were significantly down-regulated in skeletal muscle tissue of Cyp27b1 KO male mice; in contrast, the percentage of p16 and p21 myofibers, and the expression of p16, p19, p21, p53, TNFα, IL6 and MMP3 at mRNA and/or protein levels were significantly increased.

P27 deletion enhances hematopoiesis by paracrine action of IL22 secreted from bone marrow mesenchymal stem cells.

Previous studies have reported that p27 deletion stimulates the proliferation of bone marrow mesenchymal stem cells (BM-MSCs) and their differentiation into osteoblasts, it also increases bone marrow hematopoietic progenitor cells (HPCs). However, it is unknown whether the enhanced hematopoiesis induced by p27 deficiency was associated with releasing hematopoietic stem cell (HSC) and HPC supporting factors by BM-MSCs. To answer this question, we cultured the BM-MSCs from wild-type (WT) or p27 knockout (KO) mice, analyzed their proliferation, apoptosis and osteogenesis and harvested their conditioned medium (CM); We also cultured the bone marrow cells (BMCs) with normal medium or CM from WT or KO BM-MSCs and analyzed changes of HSCs and HPCs and colony forming cells (CFCs).

1,25-Dihydroxyvitamin D insufficiency accelerates age-related bone loss by increasing oxidative stress and cell senescence.

We investigated the role of insufficiency of the active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)D] in age-related bone loss. We employed mice with heterozygous deletion of , the gene encoding the enzyme that synthesizes 1,25(OH)D, as a model for 1,25(OH)D insufficiency and compared the phenotype of lumber vertebrae from 3-, 9- and 18-month-old mice and their wild-type littermates. We found that in wild-type mice, bone mineral density, bone volume, and protein expression levels decreased progressively with age, accompanied by declining osteoblastic bone formation and increasing osteoclastic bone resorption, however these age-related skeletal alterations were more severe in mice which had significantly lower serum 1,25(OH)D levels.