Marc Grynpas
PhD
Marc Grynpas, PhD is a professor in the Department of Laboratory Medicine and Pathobiology and a member of the Institute for Biomaterial and Biomedical Engineering at the University of Toronto. He is also a Senior Scientist at the Lunenfeld-Tanenbaum Research Institute of Sinai Health System and the Director of the Bone and Mineral research Group at the University of Toronto.
Dr. Grynpas graduated from the Free University of Brussels with an undergraduate degree in Physics. At the University of London, he completed his PhD in Crystallography and Biophysics on the structure of bone. After a post-doctoral fellowship at Queen Mary College (University of London) on the relation between bone structure and bone mechanical properties, he joined the laboratory of Professor Melvin Glimcher at the Children’s Hospital in Boston, which is part of the Harvard Medical School. There he worked on the nature of bone mineral and showed that amorphous calcium phosphate was not a precursor of the poorly crystalline and highly substituted apatite structure of bone mineral.
The research in his Toronto laboratory is focused on: the nature of bone mineral, animal models of osteoporosis and osteoarthritis, the effects of drugs and trace elements on bone quality and the determinants of bone fragility and bone fatigue. In addition Dr. Grynpas is part of a research group investigating tissue engineering of skeletal tissues. Most recently, Dr. Grynpas and his group have shown that vertebrate mineralization is controlled by the enzymatic formation and degradation of polyphosphates. He has supervised many Ph.D students, M.Sc Students, Post-Doctoral Fellows and 4th year undergraduate thesis.
Research Synopsis
Dr. Grynpas laboratory research is focused on: the nature of bone mineral, animal models of osteoporosis and osteoarthritis, the effects of drugs and trace elements on bone quality, the determinants of bone fragility and bone fatigue. He is also part of a research group investigating tissue engineering of skeletal tissues.
The Grynpas Laboratory is situated in the Lunenfeld-Tanenbaum Research Institute of Sinai Healthy System on the 4th Floor of the TCP building at 25 Orde Street. The laboratory includes separate areas for biomechanics, histology and image analysis as well as a general laboratory and dedicated student rooms. Currently there are 4 MSc, 5 Ph.D., and 1 Co-op students as well as 1 postdoc and 2 fellows. There is a collegial atmosphere and monthly lab meetings.
Dr. Marc Grynpas’ research focuses on the structure, chemistry and biology of the skeleton. His work covers basic research on biological mineralization to translational research on bone fragility in osteoporosis.
Tissue engineering of skeletal tissue: Dr. Grynpas, in collaboration with Drs. Pilliar, and Kandel is investigating new materials for skeletal tissue engineering. They have developed porous calcium-polyphosphates (CPP) materials as biodegradable implants which can be used as bone replacement and to anchor in vitro-formed cartilage tissue. His work explores the relationship between tissue ingrowth and material degradation of these tissue engineering constructs both in vitro and in vivo.
More recently, he has developed in collaboration with Drs. Santerre and Pilliar an interpenetrating phase composite (IPC) where a polymer infiltrates the CPP and a binder is added. This patented material will permit will permit the fabrication of plates and screws for orthopedic and dental applications.
Development of new drug for osteoporosis and bone fractures: This project addresses a critical medical need for a treatment which can reverse the effects of osteoporosis. Together with Dr Young (Simon Fraser University) we have discovered and demonstrated a novel method for targeted in vivo delivery of proven anti-resorptive bisphosphonates (BPs) together with EP4 selective receptor agonists which are proven effective for stimulating new bone growth. These conjugates drugs provide a synergistic treatment which avoids the unacceptable systemic side effects of the EP4 agonists.
We have demonstrated in an ovariectomized (OVX) rat model of osteoporosis that these conjugated drugs can induce de novo bone formation even in mature animals. We are pursuing this approach to show that we can locally augment bone where it is needed as in the jaw, where in the elderly there is not enough bone to support implants.
Biomineralization: Recently, his research group has developed a new theory showing how enzymatic control of polyphosphate synthesis and degradation explain how bone mineralization is controlled in the skeleton. Our bones are continuously remodeled throughout life, and the process of bone mineral resorption and bone mineral formation must be tightly regulated to prevent pathological calcification of soft tissue. His work has demonstrated how calcium-polyphosphate granules help prevent unwanted deposition of Ca-P04 mineral and help bone mineral formation where it is needed.
Determinants of bone quality: His research goal is to understand how bone quality changes with age and disease leads to bone fragility and fractures. He has shown that excessive increases in mineralization in humans can cause bone brittleness. He has studied the long term effects of drugs and trace elements on bone. In particular, he has found that the skeleton’s reaction to fluoride is both dose-dependent and determined by genetic factors. He is investigating sex and age differences in bone adaptation.
Animal models of Osteoporosis and Osteoarthritis: He has shown that the aging primate develops spontaneous osteoarthritis (OA) in a manner similar to humans. Because this model mimics OA in humans, it may be very useful in understanding the etiology of this disease. He has also investigated aging changes in the primate skeleton, which make it an ideal model for the aging human skeleton Also through interventions such as ovariectomy, and excess sex steroid in the monkey, he has demonstrated how this model can be used to study bone quality (bone mineralization, architecture and mechanical properties) in osteoporosis.
Diabetes and other disorders involving the skeleton: Dr Grynpas’ work extends beyond osteoporosis. In collaboration with Drs. Drucker and Fantus, he is studying the effect of Type 2 diabetes on the skeleton. While people with Type 2 diabetes have a high bone mass, they are highly susceptible to limb fractures, as distinct from osteoporotic fractures. His laboratory is studying rodent models of Type 2 diabetes to understand the mechanism by which diabetic skeletons suffer from limb fractures. In addition, together with Dr. Mitchell he is investigating the effects of gluco-corticoids on the skeleton of children with Duchenne muscular dystrophy. He has shown how bisphosphonates can prevent bone deterioration without affecting the muscle in this rare pediatric disorder.
Selected Publications
Elevated Gα11 expression in osteoblast lineage cells promotes osteoclastogenesis and leads to enhanced trabecular bone accrual in response to pamidronate. Dela Cruz A, Grynpas MD, Mitchell J. Am J Physiol Endocrinol Metab. 2016 Mar 22:ajpendo.00049.2016. doi: 10.1152/ajpendo.00049.2016. [Epub ahead of print]
Systemic mesenchymal stromal cell transplantation prevents functional bone loss in a mouse model of age-related osteoporosis. Kiernan J, Hu S, Grynpas MD, Davies JE, Stanford WL. Stem Cells Transl Med. 2016 Mar 17. pii: sctm.2015-0231. [Epub ahead of print]
Calcium polyphosphate particulates for bone void filler applications. Pilliar RM, Kandel RA, Grynpas MD, Theodoropoulos J, Hu Y, Allo B, Changoor A. J Biomed Mater Res B Appl Biomater. 2016 Feb 1. doi: 10.1002/jbm.b.33623. [Epub ahead of print]
Positive effects of bisphosphonates on bone and muscle in a mouse model of Duchenne muscular dystrophy. Yoon SH, Sugamori KS, Grynpas MD, Mitchell J. Neuromuscul Disord. 2016 Jan;26(1):73-84. doi: 10.1016/j.nmd.2015.09.015. Epub 2015 Oct 1.
Adynamic bone decreases bone toughness during aging by affecting mineral and matrix. Ng AH, Omelon S, Variola F, Allo B, Willett TL, Alman BA, Grynpas MD. J Bone Miner Res. 2016 Feb;31(2):369-79. doi: 10.1002/jbmr.2702. Epub 2015 Oct 6.
In vivo effects of two novel ALN-EP4a conjugate drugs on bone in the ovariectomized rat model for reversing postmenopausal bone loss. Hu S, Liu CC, Chen G, Willett T, Young RN, Grynpas MD. Osteoporos Int. 2016 Feb;27(2):797-808. doi: 10.1007/s00198-015-3284-x. Epub 2015 Aug 14.
Bone marrow stress decreases osteogenic progenitors. Ng AH, Baht GS, Alman BA, Grynpas MD. Calcif Tissue Int. 2015 Nov;97(5):476-86. doi: 10.1007/s00223-015-0032-3. Epub 2015 Jul 29.
Deletion of filamin A in monocytes protects cortical and trabecular bone from post-menopausal changes in bone microarchitecture. Goldberg S, Glogauer J, Grynpas MD, Glogauer M. Calcif Tissue Int. 2015 Aug;97(2):113-24. doi: 10.1007/s00223-015-9994-4. Epub 2015 Apr 17.
Effect of potassium citrate on calcium phosphate stones in a model of hypercalciuria. Krieger NS, Asplin JR, Frick KK, Granja I, Culbertson CD, Ng A, Grynpas MD, Bushinsky DA. J Am Soc Nephrol. 2015 Dec;26(12):3001-8. doi: 10.1681/ASN.2014121223. Epub 2015 Apr 8.
Long-term effects of castration on the skeleton of male rhesus monkeys (Macaca mulatta). Kessler MJ, Wang Q, Cerroni AM, Grynpas MD, Gonzalez Velez OD, Rawlins RG, Ethun KF, Wimsatt JH, Kensler TB, Pritzker KP. Am J Primatol. 2016 Jan;78(1):152-66. doi: 10.1002/ajp.22399. Epub 2015 Mar 16.
Macrophages promote osteoblastic differentiation in-vivo: implications in fracture repair and bone homeostasis. Vi L, Baht GS, Whetstone H, Ng A, Wei Q, Poon R, Mylvaganam S, Grynpas M, Alman BA. J Bone Miner Res. 2015 Jun;30(6):1090-102. doi: 10.1002/jbmr.2422.
Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone. Saito M, Grynpas MD, Burr DB, Allen MR, Smith SY, Doyle N, Amizuka N, Hasegawa T, Kida Y, Marumo K, Saito H. Bone. 2015 Apr;73:8-15. doi: 10.1016/j.bone.2014.11.025. Epub 2014 Dec 5.
Novel EP4 receptor agonist-bisphosphonate conjugate drug (C1) promotes bone formation and improves vertebral mechanical properties in the ovariectomized rat model of postmenopausal bone loss. Liu CC, Hu S, Chen G, Georgiou J, Arns S, Kumar NS, Young RN, Grynpas MD. J Bone Miner Res. 2015 Apr;30(4):670-80. doi: 10.1002/jbmr.2382.
Development, validation and characterization of a novel mouse model of Adynamic Bone Disease (ABD). Ng AH, Willett TL, Alman BA, Grynpas MD. Bone. 2014 Nov;68:57-66. doi: 10.1016/j.bone.2014.07.037. Epub 2014 Aug 8.
Can OP-1 stimulate union in a rat model of pathological fracture post treatment for soft tissue sarcoma? Nicholls F, Ng AH, Hu S, Janic K, Fallis C, Willett T, Grynpas M, Ferguson P. J Orthop Res. 2014 Oct;32(10):1252-63. doi: 10.1002/jor.22661.Epub 2014 Jun 25.