Molecular Musculoskeletal

 

Weiping Qin, MD, PhD

weiping.qin@va.gov

Dr. Qin received his MD degree from Fujian Medical University, China, in 1987, and his Ph.D. degree from Kanazawa University, Japan, in 2001. Between 2001 and 2007, Dr. Qin began his research career performing molecular biological studies in neurosciences related to neurodegenerative diseases at the Mount Sinai School of Medicine, with particular focus on altered transcriptional regulation. Dr. Qin joined the SCDRC as an investigator in 2007.  In his initial years at the Center, Dr. Qin worked closely with Dr. Cardozo on work that addressed the effects of androgens on muscle atrophy induced by glucocorticoids, denervation, and SCI. These studies have demonstrated several new mechanisms of androgen action in attenuating skeletal muscle atrophy that included activation of calcineurin, upregulation of PGC1a, downregulation of FOXO1, as well as reciprocal regulatory interaction between calcineurin and mTORC1 (two important cellular signaling pathways) in regulation of muscle cell growth.

With the increasing interest on other important medical problems (e,g., skeletal bone loss and its relation to muscle homeostasis, neuronal death, and neurological dysfunction) that develop after spinal cord injury, over the past few years Dr. Qin has successfully initiated and led an innovative research program with the objective of identifying novel treatment options for neuromusculoskeletal disorders due to spinal cord injury and exploring underlying molecular mechanisms, with a focus on osteocytes.  In this endeavor, he has developed extensive collaborations with a number of the scientists and clinicians across the country and internationally. The line of research that Dr. Qin and his team are conducting has been continuously supported by Department of Defense and VA RR&D Merit Awards.  Dr. Qin is an Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai. His recent research has been highlighted by Department of Defense SCIRP website:

 http://cdmrp.army.mil/scirp/research_highlights/14qin_highlight.shtml .

Program goals (Lay)
Spinal cord injury is associated with a variety of medical complications, including weakened bone with an increased risk for fracture and muscle loss. Dr. Qin is using small animals to model the effect of spinal cord injury on bone loss. Using this pre-clinical approach, he is performing laboratory work to study skeletal problems and nerve damage associated with spinal cord injury. His research interests include the development of novel pharmacological and non-pharmacological interventions (for example, vibration, electrical stimulation, antibodies, male sex hormone, as well as nanomedicine-based approaches), and he is exploring related mechanisms for these adverse changes and the benefit of interventions on molecular and cellular levels.

Program goals (Scientific)
Unloading, injuries to the nervous system and hormonal disorders after spinal cord injury cause one of the most rapid and marked forms of bone loss associated with an increased life-long risk of pathologic fractures, related morbidity, and financial burden. At present, there is no effective treatment to prevent or delay the marked bone loss due to spinal cord injury. To address these challenges, Dr. Qin has started and led an exciting and innovative program of research within the SCDRC, aimed at identifying potential novel treatments for such bone loss and studying not only the mechanisms by which bone loss occurs after spinal cord injury but also the mechanisms underlying beneficial effects of interventions. One particular interest is to study the function of osteocytes in these events.

Functional electrical stimulation of skeletal muscle has been shown to ameliorate bone loss after spinal cord injury, however, the molecular and cellular mechanisms underlying benefitial actions of electrical stimulation are not yet known. One project that Dr. Qin has developed will determine how electrical stimulation of muscle alters the rates of bone formation and resorption and the properties of bone cells. In a rat model of spinal cord injury, Dr. Qin and his team found that electrical stimulation induced rapid normalization of parameters of bone resorption and stimulation of bone formation associated with upregulation in osteoblasts of genes for Wnt signaling.

Partnering with Amgen, Inc., Dr. Qin and Drs. Bauman and Cardozo have recently evaluated the efficacy of an anti-sclerostin antibody to prevent bone loss after spinal cord injury in rats. The findings to date have established sclerostin antibodies as the first agent to reduce the dramatic bone loss that ensues after acute motor-complete spinal cord injury through potent anabolic actions.  In a related study, they found that a knockout of the SOST gene (encoding sclerostin protein) prevented osteoporosis in mice after spinal cord injury. The work on sclerostin inhibition has immediate and tremendous translational potential.  In addition, the finding on osteocyte biology in immobilization (such as that due to spinal cord injury) is the first to have demonstrated dramatic changes in osteocyte morphology and structure that have a profound impact on our understanding of how immobilization of any type influences this critical bone cell.

Dr. Qin is also leading another collaborative project of potential high impact aimed at improving clinical bone care after spinal cord injury by applying low intensity vibration. The results from the first phase of this study indicate that low intensity vibration improves selected biomarkers of bone turnover and gene expression while reducing osteoclastogenesis. As a next step, Dr. Qin and his team will also investigate whether other pharmacological interventions can enhance the effects of low intensity vibration on bone.

One of Dr. Qin’s recent studies has demonstrated that androgens reduce bone loss after spinal cord injury in a rat model, suggesting one potential practical modality as a clinical intervention. Related mechanistic studies suggest that spinal cord injury causes a down-regulation Wnt signaling pathway, and nandrolone (a synthetic androgen) can activate Wnt signaling and, thereby, protect against spinal cord injury-induced bone loss. This work was recently highlighted on the Department of Defense SCIRP program.

In addition to Dr. Qin’s work on bone, he has more recently developed two additional research directions. The first is to study neuroprotection and functional recovery after spinal cord injury. Spinal cord injury is a catastrophic medical problem that causes loss of sensory, motor, and autonomic function. To date, despite tremendous efforts made to the contrary, there are no fully restorative therapies for spinal cord injury. In collaborating with other scientists, Dr. Qin is currently employing a novel cutting-edge nanomedicine approach to develop better therapeutics for neuroprotection after acute spinal cord injury.

Muscle and bone are anatomically connected and function together as a physiological unit. Dr. Qin is studying the molecular basis of the interaction between muscle and bone. He and his collaborators are investigating the role of microRNAs in a process which ensures that the bone is regulated in coordination with muscle. It is anticipated that this research will provide opportunities that may not only lead to the identification of certain factors (e.g., microRNA) as novel therapeutic targets for both muscle loss and osteoporosis in individuals with spinal cord injury or the aging population, but also provide novel insights into basic physiology.


 

Research

Relevant Publications

  1. Qin W, Li X, Cao J, Peng YZ, Feng J, Collier L, Li JL, Ke HZ, Bauman WA, Cardozo C. Sclerostin Antibody Preserves the Morphology and Structure of Osteocytes and Blocks the Severe Skeletal Deteriorations after Motor-complete Spinal Cord Injury in Rats. Journal of Bone Mineral Research. 2015 May 12. doi: 10.1002/jbmr.2549. [Epub ahead of print].

http://www.ncbi.nlm.nih.gov/pubmed/25974843

Bramlett HM, Dietrich D, Marcillo A, Mawhinney LJ, Furones-Alonso O, Bregy A, Peng Y, Wu Y, Pan J, Wang J, Guo XE, Bauman WA, Cardozo C, and Qin W.  Effects of low intensity vibration on bone and muscle in rats with spinal cord injury. Osteoporosis International. 2014 Sep;25(9):2209-19.
http://www.ncbi.nlm.nih.gov/pubmed/24861907   

  • Sun L, Pan J, Peng YZ, Wu Y, Li J, Liu X, Qin YW, Bauman WA, Cardozo CP, Zaidi M, Qin W. Anabolic steroids reduce spinal cord injury-related bone loss in rats associated with increased Wnt signaling. The Journal of Spinal Cord Medicine. 2013 Nov;36(6):616-22.

http://www.ncbi.nlm.nih.gov/pubmed/3831322

  • Qin W, Sun L, Cao J, Peng Y, Collier L, Wu Y, Creasey G, Li J, Qin Y, Jarvis J, Bauman WA, Zaidi M, Cardozo C. The Central Nervous System (CNS)-independent Anti-bone-resorptive Activity of Muscle Contraction and the Underlying Molecular and Cellular Signatures. J Biol Chem. 2013;288(19):13511-21.

http://www.ncbi.nlm.nih.gov/pubmed/23530032

  • Qin W, Bauman WA, Cardozo C. Bone and muscle loss after spinal cord injury: organ interactions. Ann NY Acad Sci. 2010;1211:66-84.

http://www.ncbi.nlm.nih.gov/pubmed/21062296

  • Qin W, Bauman WA, Cardozo C. Evolving Concepts in Neurogenic Osteoporosis. Curr Osteoporos Rep. 2010;8(4):212-8.

http://www.ncbi.nlm.nih.gov/pubmed/20820963

For a full listing of publications, please see:

http://www.ncbi.nlm.nih.gov/sites/myncbi/1P5jFRUis6Q5G/bibliography/40205437/public/?sort=date&direction=ascending