Premium
DELETION OF MBTPS1 IN BONE LEADS TO ENHANCEMENT OF MUSCLE MASS AND FUNCTION IN MATURE MICE
Author(s) -
Gorski Jeffrey,
Huffman NT,
Breggia Anne,
Rosen Cliff J.,
Chittur Sridar V.,
Stern Amber,
Dallas Mark,
Seidah N G,
Brotto Leticia,
Bonewald Lynda F.,
Brotto Marco
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.942.3
Subject(s) - endocrinology , medicine , osteocyte , conditional gene knockout , leptin , skeletal muscle , cre recombinase , knockout mouse , chemistry , biology , phenotype , genetically modified mouse , transgene , osteoblast , gene , obesity , receptor , biochemistry , in vitro
Cis‐Golgi protease Mbtps1, a proprotein convertase, is responsible for activating a small family of transmembrane spanning b‐ZIP transcription factors. We previously demonstrated Mbtps1 is required for mineralization of osteoblastic cultures. To understand its role in skeletal development, we conditionally deleted MBTPS1 using osteocyte restricted DMP1 Cre recombinase. Despite the absence of an early bone phenotype, KO male mice abruptly begin to gain weight at skeletal maturity. At 40 weeks, knockout mice were 7.3g larger (p=0.034) than littermate controls. MicroCT and piximus analysis of bone and fat content cannot account for this difference in mass. Since MBTPS1 was specifically ablated in osteocytes, we initiated systematic muscle physiological studies to test our recently proposed hypothesis of a bone‐muscle crosstalk axis in health and disease. We found that the extensor digitorum longus and soleus muscles were significantly heavier and stronger in cKO mice as compared to controls. We also observed a leftward shift in their force vs. frequency relationships, suggesting that cKO muscles could be more sensitive to calcium. Interestingly, leptin was found to be 2‐fold higher in serum from cKO mice than controls (p=0.018). We postulate that MBTPS1 ablation in osteocytes leads to augmented serum levels of leptin that acts systemically to alter muscle function. Support: NIH‐NIA P01 AG039355 and MOLSRB.