The main objectives of this proposal are: to increase the research skills of the applicant and to enhance the current understanding of how passive stretch may induce long term, structural cellular changes in muscle. The rehabilitation of patients with soft tissue contractures frequently involves the use of passive stretch. However a scientific rationale which might explain increased mobility after the application of passive stretch is lacking. The career development plan for the applicant includes a combination of coursework and hands-on laboratory experience focusing on increasing the applicant's expertise in molecular biology. Mentoring is achieved by a multidisciplinary research advisory committee which includes both clinicians (orthopaedic surgeons) and basic scientists with expertise in muscle biophysics, membrane biology and molecular biology. The research plan proposes to study the effects of passive stretch in a mammalian skeletal muscle cell culture. The central hypothesis is that stretch is perceived by the muscle fiber as a stimulatory signal and ultimately leads to myofibrillogenesis. Experiments are proposed to evaluate the role of the cytoskeleton and associated molecules, such as integrins, in the signaling mechanism and in organizing contractile structures. The following hypothesis will be tested: 1. Passive stretch enhances myoblast proliferation and subsequent myotube formation. 2. Passive stretch is a signal for cytoskeletal remodeling and ultimately for myofibrillogenesis. 3. Passive stretch regulates the mRNA and/or protein synthesis of cytoskeletal and cytoskeleton-related molecules 4. Passive stretch induces tyrosine phosphorylation of integrins.
The specific aims for this proposal are: 1. To determine the degree of proliferation, the rate of fusion, and the maturation of cultured mammalian skeletal myoblast/myofibers exposed to various regimens of passive stretch by using established cell biological and immunological methods. 2. To determine changes in the cellular location of cytoskeletal molecules (protein and mRNA) in cultured mammalian skeletal muscle fibers in response to stretch by using confocal immunofluorescent microscopy and in situ hybridization. 3. To determine whether passive stretch increases the expression of genes encoding cytoskeletal and cytoskeleton-related proteins by using western and northern blot analysis. 4. To elucidate whether tyrosine phosphorylation occurs as a result of passive stretch by using immunoprecipitation and western blot analysis. The results of this approach will be used to enhance the scientific basis of passive stretch as a rehabilitation technique. Ultimately this research should lead to improved treatments for patients with soft tissue contractures.

Project Start
1998-09-01
Project End
2003-05-30
Budget Start
1998-09-01
Budget End
1999-05-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Surgery
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Lovering, Richard M; Roche, Joseph A; Bloch, Robert J et al. (2007) Recovery of function in skeletal muscle following 2 different contraction-induced injuries. Arch Phys Med Rehabil 88:617-25
Hakim, Marc; Hage, William; Lovering, Richard M et al. (2005) Dexamethasone and recovery of contractile tension after a muscle injury. Clin Orthop Relat Res 439:235-42
Lovering, Richard M; Hakim, Marc; Moorman 3rd, Claude T et al. (2005) The contribution of contractile pre-activation to loss of function after a single lengthening contraction. J Biomech 38:1501-7
De Deyne, Patrick G; Hafer-Macko, Charlene E; Ivey, Frederick M et al. (2004) Muscle molecular phenotype after stroke is associated with gait speed. Muscle Nerve 30:209-15
Lovering, Richard M; De Deyne, Patrick G (2004) Contractile function, sarcolemma integrity, and the loss of dystrophin after skeletal muscle eccentric contraction-induced injury. Am J Physiol Cell Physiol 286:C230-8
Gonzalez-Serratos, Hugo; Chang, Ruzhang; Rozycka, Monika et al. (2003) Role of the T-system and the Na-K pump on fatigue development in phasic skeletal muscle. Adv Exp Med Biol 538:543-55; discussion 555
De Deyne, Patrick G (2002) Lengthening of muscle during distraction osteogenesis. Clin Orthop Relat Res :S171-7
De Deyne, P G; Kinsey, S; Yoshino, S et al. (2002) The adaptation of soleus and edl in a rat model of distraction osteogenesis: IGF-1 and fibrosis. J Orthop Res 20:1225-31
De Deyne, P G (2001) Application of passive stretch and its implications for muscle fibers. Phys Ther 81:819-27
Hayatsu, K; De Deyne, P G (2001) Muscle adaptation during distraction osteogenesis in skeletally immature and mature rabbits. J Orthop Res 19:897-905