Macrophages commit postnatal endothelium-derived progenitors to angiogenesis and restrict endothelial to mesenchymal transition during muscle regeneration.

The damage of the skeletal muscle prompts a complex and coordinated response that involves the interactions of many different cell populations and promotes inflammation, vascular remodeling and finally muscle regeneration. Muscle disorders exist in which the irreversible loss of tissue integrity and function is linked to defective neo-angiogenesis with persistence of tissue necrosis and inflammation. Here we show that macrophages (MPs) are necessary for efficient vascular remodeling in the injured muscle. In particular, MPs sustain the differentiation of endothelial-derived progenitors to contribute to neo-capillary formation, by secreting pro-angiogenic growth factors. When phagocyte infiltration is compromised endothelial-derived progenitors undergo a significant endothelial to mesenchymal transition (EndoMT), possibly triggered by the activation of transforming growth factor-ß/bone morphogenetic protein signaling, collagen accumulates and the muscle is replaced by fibrotic tissue. Our findings provide new insights in EndoMT in the adult skeletal muscle, and suggest that endothelial cells in the skeletal muscle may represent a new target for therapeutic intervention in fibrotic diseases.

Examination of telomere lengths in muscle tissue casts doubt on replicative aging as cause of progression in Duchenne muscular dystrophy.

The mean telomere length (TL) of somatic cells indicates their replicative age. In comparison with normal leukocytes (-0.03 kbp/y, 6.2 kbp at 80 y), we found advanced TL shortening in premature aging due to ataxia-telangiectasia or the Nijmegen chromosomal breakage syndrome. Duchenne muscular dystrophy (DMD) has been related to replicative senescence of satellite cells (SCs) caused by increased fiber turnover. Therefore, we determined TLs in DMD muscle. Because the regenerated fiber nuclei are produced by SCs. telomeres of both fiber and SC nuclei should be shortened. In DMD the SC number is increased. We determined that up to the age of 7 y the sum of fiber and SC nuclei should be large enough (73%) for the detection of TL shortening. Normal muscle fibers have negligible turnover rates, and, as expected, we did not find age-related TL shortening (10-83 y, n = 24, 8.3 +/- 0.5 kbp). Surprisingly, there was only slight TL shortening in patient muscles (DMD, 0.3-4.8 y, n = 4, 8.3 +/- 0.7 kbp; 5-7 y, n = 7, 7.9 +/- 0.4 kbp; limb-girdle muscular dystrophy 2C, 13 y, 7.6 kbp; Becker muscular dystrophy, 7 y, 8.5 kbp). Similarly, the peak positions of the telomere blots varied only slightly (DMD, 10.0 +/- 0.9 kbp; normal: 10.7 +/- 0.9 kbp). In accordance with our TL findings we derived less than 4 annual doublings per SC from published histologic data on DMD.

Wheat kernel ingestion protects from progression of muscle weakness in mdx mice, an animal model of Duchenne muscular dystrophy.

A simple, reproducible test was used to quantify muscle weakness in mdx mice, an animal model of Duchenne muscular dystrophy. The effect of bedding on wheat kernels and of dietary supplementation of alpha-tocopherol on the progression of muscle weakness was investigated in mdx mice. When measured during the first 200 d of life, mdx mice developed muscle weakness, irrespective of bedding and diet. When kept on wood shavings and fed a conventional rodent diet, mdx mice showed progressive muscle weakness over the consecutive 200 d, and eventually showed a significant weight loss during the next 200-d observation period. Progression of muscle weakness and weight loss were almost completely prevented in mdx mice that were kept on wheat kernel bedding. In contrast, only incomplete maintenance of muscle strength and body weight was observed in mdx mice kept on wood shavings and fed the alpha-tocopherol-supplemented diet. It is concluded from these experiments that a component of wheat kernels other than alpha-tocopherol is essential to prevent the progression of muscle weakness in mdx mice.

The migrant farmworker: health care challenge.

Migrant farmworkers comprise a severely medically underserved population, both nationally and in New Jersey. This article defines the migrant population, reviews their specific health problems, and illustrates the urgent need for the medical community's attention and resources.