The Transgenic and Mechanical Loading Core will support various aspects of all subprojects within the Program Project Grant and is vital to the success of each. The major goal of tills Program Project Grant proposal is to understand the mechanism underlying crosstalk signaling between muscle and bone. A central theme (hypothesis) of all the projects Is that cross talk signaling is a critical component of maintaining the architectural, material and biomechanical properties of bone and the ability of the osteocyte to respond to load. Reciprocally we will determine If osteocyte derived factors alter the functionality of muscle cells and osteoblasts. The overarching goal of this Program Project Grant is to determine if(how) aging alters these bone properties and/or if aging alters the intrinsic ability of the osteocyte to respond to load and to signal to muscle cells and osteoblasts. The Specific Alms of this Core are:
Aim 1 : provide mice of the correct sex, genotype and age for the experiments described in Projects 1,2, 3,4.
Aim 2 : perform in vivo mechanical loading studies for Projects 1 and 4 as needed on the various mouse lines.
Aim 3 : perform ex vivo mechanical testing to assess the material and biomechanical properties of bones in the various lines of mice needed for Projects 1 and 4.
Aim 4 : perform and support in vitro fluid flow studies on isolated bone cells and cell lines as a model for testing in vitro the effects of fluid flow induced loading of these cells In Projects 1,2, 3,4. Currently experiments are proposed using 15 different lines of wildtype, transgenic or knockout mice and this Core will provide the necessary numbers of appropriate genotype, sex and aged mice in support of the studies in the four subprojects. In addition, new transgenic and/or knockout mouse lines will be created or acquired through this core such as the Sost-ERT2-Cre, Sost-tg and Myogenin-Cre mouse lines. Both in vivo and in vitro mechanical loading studies, and all biomaterial and biomechanical assessments needed to guide the studies proposed in the various projects, will be performed using the equipment and resources of this core. This core centralization will provide maximum efficiency and cost-effectiveness in the conduct of the proposed studies.
This Core will provide centralized support for all subprojects within this Program Project whose goal is to understand the mechanisms underlying crosstalk signaling between muscle and bone and how this is altered by aging. The Core is critical to the success of each of the projects and has the potential to be paradigm changing and result In new targets for drug development for the treatment of osteoporosis and sarcopenia.
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|Jähn, Katharina; Kelkar, Shilpa; Zhao, Hong et al. (2017) Osteocytes Acidify Their Microenvironment in Response to PTHrP In Vitro and in Lactating Mice In Vivo. J Bone Miner Res 32:1761-1772|
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|Farr, Joshua N; Fraser, Daniel G; Wang, Haitao et al. (2016) Identification of Senescent Cells in the Bone Microenvironment. J Bone Miner Res 31:1920-1929|
|Gorski, Jeff P; Huffman, Nichole T; Vallejo, Julian et al. (2016) Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) Gene in Osteocytes Stimulates Soleus Muscle Regeneration and Increased Size and Contractile Force with Age. J Biol Chem 291:4308-22|
|Zhu, Meiling; Sun, Ben-Hua; Saar, Katarzyna et al. (2016) Deletion of Rac in Mature Osteoclasts Causes Osteopetrosis, an Age-Dependent Change in Osteoclast Number, and a Reduced Number of Osteoblasts In Vivo. J Bone Miner Res 31:864-73|
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