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Crosstalk between Bone and Muscle: Deletion of Mbtps1 in Bone Leads to Age‐Dependent Increase in Muscle Size and Contractile Function
Author(s) -
Gorski Jeffrey,
Huffman Nichole,
Seidah Nabil,
Bonewald Lynda,
Brotto Marco
Publication year - 2015
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.29.1_supplement.495.2
Subject(s) - osteocyte , myosin , endocrinology , soleus muscle , medicine , conditional gene knockout , chemistry , osteoblast , immunostaining , anabolism , skeletal muscle , microbiology and biotechnology , biology , phenotype , immunohistochemistry , in vitro , biochemistry , gene
Proprotein convertase Mbtps1 is required for transcription of bone matrix proteins including fibronectin, collagen XI, and PHEX by osteoblastic/osteocytic cells. Since complete loss of Mbtps1 is lethal at E4, we asked if conditional deletion of Mbtps1 using early osteocyte DMP1 cre would disrupt bone structure. Mbtps1 cKO male mice were slightly larger than controls (43.6 g vs. 40.2 g, p=0.057) but displayed no significant changes in bone dimensions, BMD, mineral content, or cortical/trabecular bone parameters at 12 and 40 weeks of age. However, 40 week old soleus muscles from cKO mice weighed 20% more and contracted with 50% more force ex vivo even when normalized for size despite the fact that Mptps1 expression was unchanged (0.94 cKO/control +/‐ 0.42 STD). Immunostaining revealed cKO soleus muscles contained about 35% type I and 60% type 2 myosin heavy chain positive cells, were devoid of myosin 2b fiber+ cells which comprised 5% of control cells, and displayed a higher percentage of central nuclei than controls. Central nuclei, which can reflect muscle repair or regeneration, were restricted to type I myosin heavy chain positive cells. The osteocyte specific deletion of Mbtps1 along with genome arrays that demonstrate increased expression of muscle performance markers such as α‐actinin3 support a cross‐talk signaling mechanism by which Mbtps1‐deficient bone cells increase muscle contractile function in adult mice. Revealing the molecular mechanism responsible could lead to new therapies for a host of muscle disorders.