Stephen Sims

Professor

Stephen Sims

PH.D. McMaster University
B.Sc. University of Western Ontario
Office:  Dental Sciences Building 0073
Phone: (519) 661-2111 Ext. 83768
Fax:  (519) 661-3827
E-mail: stephen.sims@schulich.uwo.ca
See Publications by Stephen Sims on PubMed

Stephen SimsDr. Sims is a cellular physiologist with expertise in ion channels and signaling in skeletal and muscle cells.  Just as knowledge of ion channels and [Ca2+]i is essential for understanding the physiology and pathology of nerve and muscle, such information is instrumental for understanding control of osteoclasts, the cells responsible for the resorption of bone.

Scanning electron micrograph shows resorption pits caused by the action of osteoclasts resorbing the mineral substrate.

Stephen Sims

We use a combination of experimental methods, including digital fluorescence imaging using Ca2+-sensitive fluorescent dyes to monitor regional changes of calcium in muscle and bone cells.  We also carry out patch clamp recording to monitor membrane currents and their regulation. 

Osteoclasts are large multinucleated cells with extensive lamellipodia.

Understanding the cell biology of osteoclasts is essential for the rational development of therapies directed at arresting the loss of bone in inflammatory and metabolic diseases of bones and joints. 

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Stephen SimsProposed mechanism of LPA signaling in osteoclasts. LPA is released by neighboring osteoblasts and binds to LPA receptors on an osteoclast. Binding of LPA to LPA1 activates receptor to induce elevation of cytosolic free calcium, activation of NFAT and enhancement of survival. Binding of LPA also causes cytoskeletal changes. This research was originally published in The Journal of Biological Chemistry. Lapierre et al. Lysophosphatidic acid signals through multiple receptors in osteoclasts to elevate cytosolic calcium concentration, evoke retraction, and promote cell survival. J Biol Chem. 2010; 285, 25792-25801. © the American Society for Biochemistry and Molecular Biology. doi: 10.1074/jbc.M110.109322.

The studies have relevance to understanding osteoclast activity in diseases such as rheumatoid arthritis, where osteoclasts are found at the pannus/bone interface and are responsible for loss of subchondral and periarticular bone.  The destruction of bone and calcified cartilage contributes to the pain, progressive deformity and disability associated with this disease.  Ion channels and receptors on osteoclasts represent targets for intervention in diseases such as rheumatoid arthritis.

Trainees under his supervision have won local, national and international awards for their research, and have progressed to independent careers in academia, education, medicine, dentistry and financial markets.

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Lapierre DM, Tanabe N, Pereverzev A, Spencer M, Shugg RP, Dixon SJ, Sims SM. Lysophosphatidic acid signals through multiple receptors in osteoclasts to elevate cytosolic calcium concentration, evoke retraction and promote cell survival. Journal of Biological Chemistry 285: 25792-25801, 2010. 

Durand M, Boire G, Komarova SV, Dixon SJ, Sims SM, Harrison RE, Nabavi N, Maria O, Manolson MF, Mizianty M, Kurgan L, de Brum-Fernandes AJ. The increased ex vivo osteoclastogenesis in patients with rheumatoid arthritis is due to increased number of precursors and decreased apoptosis - the in vitro osteoclast differentiation in arthritis (IODA) study.  Bone. 48: 588-596, 2011.

Espinosa-Tanguma R, O’Neil C, Chrones T, Pickering JG, Sims SM. Essential role for calcium waves in migration of human vascular smooth muscle cells. American Journal of Physiology (Heart and Circulation) 301: H315-H323, 2011.

Tanabe N, Wheal BD, Kwon J, Chen HH, Shugg RPP, Sims SM, Goldberg HA, Dixon SJ. Osteopontin signals through calcium-NFAT in osteoclasts: a novel RGD-dependent pathway promoting cell survival. Journal of Biological Chemistry.  286: 39871-39881, 2011.

Zhang T, Lu X, Li J, Chidiac P, Sims SM, Feng Q. Inhibition of Na/K ATPase promotes myocardial tumor necrosis factor-alpha protein expression and cardiac dysfunction via calcium/mTOR signaling in endotoxemia. Basic Research in Cardiology 107: 254-266, 2012.

Durand M, Komarova SV, Bhargava A, Li K, Fiorino C, Nabavi N, Manolson MF, Harrison RE, Dixon SJ, Sims SM, Mizianty MJ, Kurgan L, Boire G, Lucena-Fernandes M, de Brum-Fernandes A. Monocytes from patients with osteoarthritis display increased osteoclastogenesis and bone resorption: the in vitro osteoclast differentiation in arthritis (IODA) study. MS ID# ar-11-1887. Arthritis and Rheumatism. Oct 8. doi: 10.1002/art.37722. [Epub ahead of print] 2012.

Sims SM, Panupinthu N, Lapierre DM, Pereverzev A, Dixon SJ. Lysophosphatidic acid: a potential mediator of osteoblast-osteoclast signaling in bone. Biochimica et Biophysica Acta. 1831: 109-116, 2013.




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