Matthew J. Silva, Ph.D.

Orthopaedic Surgery
Associate Professor
Biomedical Engineering

Molecular Cell Biology Program
Human and Statistical Genetics Program

Research Abstract:

Skeletal Mechanobiology and Biomechanics: With aging or osteoporosis, bone mass and strength are diminished, leading to an increase in fracture risk. Mechanical loading is a powerful stimulus for formation of new bone and thus could potentially be used to enhance bone mass and strength. Our lab utilizes several in vivo mechanical loading models to examine how bones respond to increased loading. These approaches range from mild loading using whole-body vibration to fatigue loading that produces stress fractures. Our overall goals are two-fold. First, we seek to better understand the mechanical and molecular factors that regulate loading-induced bone formation. Current efforts are focused on BMP and Hedgehog signaling, and the role of angiogenesis. Second, we seek to evaluate clinically relevant loading strategies. We utilize multidisciplinary methods to assess skeletal responses in our studies, including micro-computed tomography (mCT), positron emission tomography (PET), gene expression by real-time PCR and microarray analysis, dynamic and static histomorphometry, and mechanical testing. We also make extensive use of mouse genetic models for conditional gene deletion and reporter expression. In a collaborative project, we are utilizing mouse genetic methods to identify genes that regulate bone size and strength, and that may regulate the interaction between body composition (fat) and bone properties.

Selected Publications:

Carson EA, Kenney-Hunt JP, Pavlicev M, Bouckaert K, Chinn A, Silva MJ, Cheverud JM. Weak Genetic Relationship Between Trabecular Bone Morphology and Obesity in Mice. Bone. 2012 Apr 6;51(1):46-53 2012.

Silva MJ, Brodt MD, Lynch MA, Stephens AL, Wood DJ, Civitelli R. Tibial Loading Increases Osteogenic Gene Expression and Cortical Bone Volume in Mature and Middle-Aged Mice. Tibial Loading Increases Osteogenic Gene Expression and Cortical Bone Volume in Mature and Middle-Aged Mice. PLoS ONE 7(4): e34980, 2012. [PMC3325918]

McKenzie JA, Bixby EC, Silva MJ. Differential gene expression from microarray analysis distinguishes woven and lamellar bone formation in the rat ulna following mechanical loading. PLoS ONE, 2011;6(12):e29328. [PMC3245266]

Alvarado DM, McCall K, Aferol H, Silva MJ, Garbow JR, Spees WM, Patel T, Siegel M, Dobbs MB, Gurnett CA. Pitx1 Haploinsufficiency Causes Clubfoot in Humans and a Clubfoot-like Phenotype in Mice. Human Molec Genetics, 20(20):3943-52, 2011. [PMC3177645]

Tomlinson RE, Silva MJ, Shoghi KI. Quantification of skeletal blood flow and fluoride metabolism in rats using PET in a pre-clinical stress fracture model. Molecular Imaging & Biology, 2012 Jun;14(3):348-54.

Grimston SK, Goldberg DB, Watkins M, Brodt MD, Silva MJ, Civitelli R. Connexin43 deficiency reduces the sensitivity of cortical bone to the effects of muscle paralysis. J. Bone Miner. Res. 2011 Sep;26(9): 2151-60.

Craft CS, Zou W, Watkins M, Grimston S, Brodt MD, Broekelmann TJ, Teitelbaum SL, Civitelli R, Silva MJ, Mecham RP. Microfibril-associated glycoprotein-1 (MAGP1), an extracellular matrix regulator of bone remodeling. J. Biol. Chem. 2010 285(31):23858-67. [PMC2911322]

McKenzie JA, Silva MJ. Comparing histological, vascular and molecular responses associated with woven and lamellar bone formation induced by mechanical loading in the rat ulna. Bone, 2011 48(2):250-8. [PMC3021598]

Lynch MA, Brodt MD, Stephens AL, Civitelli R, Silva MJ. Low-Magnitude Whole-Body Vibration Does Not Enhance the Anabolic Skeletal Effects of Intermittent PTH in Adult Mice. J. Orthop. Res., 2011 Apr;29(4): 465-72.

Kotiya AA, Bayly PV, Silva MJ. Short-term Low-strain Vibration Enhances Chemo-transport Yet Does Not Stimulate Osteogenic Gene Expression or Cortical Bone Formation in Adult Mice. Bone. 2011 Mar 1;48(3): 468-75. [PMC3039102]

Last Updated: 8/15/2012 9:01:54 AM

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