Skeletal Biology Laboratory

About Our Lab

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.

The Brigham and Women's Hospital Skeletal Biology 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. One of our research activities concerns the mechanisms by which osteoinductive materials, like demineralized bone matrix, induce the differentiation of chondrocytes from human skin-derived fibroblasts and mesenchymal stem cells and the potential to apply this phenomenon to various clinical applications. The current investigations of Skeletal Biology Laboratory mainly focus on neuroskeletal biology, osteoporosis in neurological disorders, and alcohol-induced osteopenia.

The Laboratory is the hub for several multidisciplinary and cross-departmental programs. 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 our discoveries on mechanisms of aging of bones and joints and bone and cartilage regeneration into innovative approaches for osteoporosis and osteoarthritis prevention and treatment. 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 elucidate the effects of age on intracellular signaling pathways and evaluate rejuvenation protocols.
• We seek to discover how the cellular microenvironment (niche) aging of skeletal stem cells may contribute to their declining ability to produce new bone-producing cells that could be important in developing methods for keeping adult stem cells healthy longer, which in turn could keep our bones healthy longer.
• We seek to understand neurodegenerative osteoporosis and alcohol-induced osteopenia from the aspect of neuroskeletal biology, an interdisciplinary field of neuroscience and bone biology.

Selected References

Zhou S, Eid K, Glowacki J. Cooperation between TGF-beta and Wnt pathways during chondrocyte and adipocyte differentiation of human marrow stromal cells. J Bone Miner Res. 2004; 19:463-70.

Zhou S, Lechpammer S, Greenberger JS, Glowacki J. Hypoxia inhibition of adipocytogenesis in human bone marrow stromal cells requires transforming growth factor-beta/Smad3 signaling. J Biol Chem. 2005; 280:22688-96.

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.

Zhou S, LeBoff MS, Glowacki J. Vitamin D metabolism and action in human bone marrow stromal cells. Endocrinology. 2010; 151:14-22.

Zhou S, Bueno EM, Kim SW, Amato I, Shen L, Hahne J, Bleiberg I, Morley P, Glowacki J. Effects of age on parathyroid hormone signaling in human marrow stromal cells. Aging Cell. 2011; 10: 780-8.

Zhou S, Glowacki J, Kim SW, Hahne J, Geng S, Mueller SM, Shen L, Bleiberg I, LeBoff MS. Clinical characteristics influence in vitro action of 1,25-dihydroxyvitamin D₃ in human marrow stromal cells. J Bone Miner Res. 2012; 27:1992-2000.

Zhou S, Mizuno S, Glowacki J. Wnt pathway regulation by demineralized bone is approximated by both BMP-2 and TGF-β1 signaling. J Orthop Res. 2013; 31:554-60.

Zhou S. Paracrine effects of haematopoietic cells on human mesenchymal stem cells. Sci Rep. 2015; 5:10573.

Zhou S, Thornhill TS, Meng F, Xie L, Wright J, Glowacki J. Influence of osteoarthritis grade on molecular signature of human cartilage. J Orthop Res. 2016; 34:454-62.

Zhou S, Glowacki J. Chronic kidney disease and vitamin D metabolism in human bone marrow-derived MSCs. Ann N Y Acad Sci. 2017; 1402:43-55.

Zhou S, Glowacki J. Dehydroepiandrosterone and Bone. Vitam Horm. 2018; 108:251-271.

Meng F, Bertucci C, Gao Y, Li J, Luu S, LeBoff MS, Glowacki J, Zhou S. Fibroblast growth factor 23 counters vitamin D metabolism and action in human mesenchymal stem cells. J Steroid Biochem Mol Biol. 2020; 199:105587

Qian D, Zhou H, Fan P, Yu T, Patel A, O'Brien M, Wang Z, Lu S, Tong G, Shan Y, Wang L, Gao Y, Xiong Y, Zhang L, Wang X, Liu Y, Zhou S. A Traditional Chinese Medicine Plant Extract Prevents Alcohol-Induced Osteopenia. Front Pharmacol. 2021; 12:754088.

Patel A, Zhou EW, O'Brien M, Wang X, Zhou S. Melatonin in neuroskeletal biology. Curr Opin Pharmacol. 2021; 61:42-48.