Skeletal Biology Laboratory

Faculty:

Fellows and Students:

Julie Glowacki, PhD, Director

Jin Li, MD
Shuanhu Zhou, PhD Fangang Meng, MD
Elaine Burke

The rapidly expanding field of skeletal biology promises to yield major treatment advances in many areas of orthopedic surgery over the next few decades. Our basic, clinical, and translational research concerns skeletal repair, skeletal tissue engineering, and normal and abnormal bone metabolism.

neocartilage
Histological section shows neo-cartilage induced by implanting Demineralized Bone Particles under the skin of a test animal. The laboratory is identifying how to apply this process to repair cartilage in patients.

The Brigham and Women’s Hospital Skeletal Biology Research Laboratory has particular interest in the study of skeletal aging, metabolic bone disease, skeletal tissue engineering, and osteoinductive materials. The scientific approaches focus on translational research, i.e., the identification of clinical problems, testing of hypotheses in relevant experimental models, and application to patient care. Innovative 3-dimensional culture devices serve as a platform technology for many of the osseous reconstructive and pathophysiological programs of research ongoing in the Laboratory. One of our major research activities concerns the mechanisms by which osteoinductive materials, like demineralized bone matrix, induce the differentiation of chondrocytes from skin-derived fibroblasts and the potential to apply this phenomenon to various clinical applications.

The Laboratory is the hub for several multidisciplinary, cross-departmental programs, especially between members of the BWH Skeletal Health and Osteoporosis Center, led by Meryl LeBoff, M.D., and clinical members of the Department of Orthopedic Surgery and the Division of Rheumatology. With multidisciplinary collaborators, the Laboratory seeks to translate new basic and clinical research into a platform for skeletal health and orthopedic care.

  • We seek to translate into innovative approaches for osteoporosis and osteoarthritis prevention and treatment our recent discoveries on mechanisms of aging of bones and joints and on bone and cartilage regeneration. This program includes stem cell, tissue engineering, and drug discovery approaches.
  • We seek to develop new ways of activating patients’ endogenous stem cells for musculoskeletal therapies.
  • We seek to apply our advances in bone and cartilage tissue engineering to problems in knee meniscal and TMJ (temporomandibular joint) disorders.
  • We seek to elucidate the effects of age on intracellular signaling pathways and to evaluate rejuvenation protocols.
  • We seek to use novel antioxidants in preclinical models of fracture healing.
  • We seek to discover risk factors for osteoporosis in patients with osteoarthritis. The development of osteoporosis in those patients was not recognized until our recent discovery from a study of patients with hip fracture.
  • We seek to discover the impact of vitamin D supplementation on progression of osteoarthritis with a combination of epidemiological, clinical, and basic mechanistic research.
  • We seek to test the impact of vitamin D and omega-3 supplements on fractures, falls, and frailty.
  • We seek to discover the impact of osteomalacia on orthopedic surgical patients. It had been presumed that this adult form of vitamin D deficiency was not a problem in the US, but our work shows its alarming prevalence in BWH trauma patients. Rigorous information is needed on how to ensure post-surgical success with vitamin D treatments.
  • We seek to discover how sharks are able to repair cartilage wounds, but humans and other species show very limited capacity to heal cartilage.
SELECTED RECENT REFERENCES:

Rosen C, Glowacki J, Bilzekian JP (eds) The Aging Skeleton, Academic Press, San Diego, CA, 1999.

LeBoff M, Kohlmeier L, Hurwitz S, Franklin J, Wright J, Glowacki J. Occult vitamin D deficiency in postmenopausal American women with acute femur fracture. J Amer Med Assoc 1999; 16:1505-1511.

Mueller SM, Glowacki J. Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges. J Cell Biochem 2001;82:583-590.

Mizuno S, Tateishi T, Ushida T, Glowacki J. Hydrostatic fluid pressure enhances matrix synthesis and accumulation by bovine chondrocytes in three-dimensional culture. J Cell Phys 2002;193:319-27.

Glowacki J, Hurwitz S, Thornhill TS, Kelley M, LeBoff ML. Osteoporosis and vitamin D deficiency among postmenopausal osteoarthritic women undergoing total hip arthroplasty. J Bone Joint Surg. 2003; 85A: 2371-2377.

Warden S, Zaleske DJ, Glowacki J. Fate of a chimeric joint construct in an ectopic site in SCID mice. Cell Transplantation 2004; 13:161-168.

Eid K, Thornhill TS, Glowacki J. Chondrocyte gene expression in osteoarthritis: Correlation with disease severity. J Orthop Res 2006;24:1062-8.

Glowacki J, Mizuno S. Collagen scaffolds for tissue engineering. Biopolymers. 89:338-344; 2008.

Zhou S, Greenberger JS, Epperly MW, Goff JP, Adler C, LeBoff MS, Glowacki J. Age-related intrinsic changes in human marrow stromal cells and their differentiation to osteoblasts. Aging Cell. 2008 7:335-343.

Glowacki J, Harris M, Simon J, Wright J, Kolatkar N, Thornhill TS, LeBoff MS. Brigham fracture intervention team (B-FIT) initiatives for hospital patients with hip fractures: A paradigm shift. Intl J Endocrin. 2009.