Janet Rubin

Janet Rubin

 

Professor

Departments of Medicine, Pediatrics & Pharmacology, Division of Endocrinology & Metabolism

M.D., Medicine
Brown University School of Medicine

Biosketch [.pdf]

Carolina Cardiovascular Biology Center

Contact Information  ->>

Research Interests

  • Mechanical control of bone remodeling
  • Mesenchymal stem cell differentiation: Osteoblast/Adipocyte
  • Osteoporosis

Research Synopsis

The skeleton is a complex tissue that is able to regulate its own mass and architecture to meet two critical and competing responsibilities: one structural and the other metabolic. The structure of bone is determined largely through its ability to respond to daily loading with intelligent remodeling. When mechanical signals are suppressed (no exercise, space travel, getting old) bone structure degenerates - and bone resorption outpaces bone formation. If skeletal degeneration is severe it will lead to catastrophic failure with fracture. Alternatively, daily skeletal loading leads to bone formation, enhancing not only the activity of bone osteoblasts to make new bone, but also promotes the entry of mesenchymal stem cells into the osteogenic lineage. Our cellular and molecular biological investigations are aimed at understanding mechanical and hormonal control of bone remodeling.

Our current primary focus is to understand the role of biophysical forces experienced by the skeleton during exercise, in controlling bone remodeling. We are interested in signaling events that enhance osteoblast activity - in particular the ability of mechanical factors to activate MAPK, beta-catenin and NFATc1. These signals appear to have regulatory roles not only in promoting bone formation and inhibiting bone resorption, but also in preventing mesenchymal stem cell entry into the adipocyte lineage. Other signals which appear to have important roles in promoting bone function and repressing fat function include COX2, nitric oxide, IGF-1 and vitamin D. Eventually we hope to be able to apply this understanding to improving bone structure by using non-pharmacologic strategies.

Publications

pubmed

Click above for PubMed publications.

  • Case, N., Ma, M., Sen, B., Xie, Z., Gross, T.S., and Rubin, J. (2008) β-catenin levels influence rapid mechanical responses in osteoblasts. J Biol Chem 283: 29196-205. Abstract
  • Sen, B., Xie, Z., Case, N., Ma, M., Rubin, C.T., and Rubin, J. (2008) Mechanical strain prevents adipogenesis in mesenchymal stem cells by stimulating a durable β-catenin signal. Endocrinology 149: 6065-75. Abstract
  • Rubin, J. and Rubin, C.T. (2008) Commentary: Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones. Journal of Bone and Mineral Research 23: 1369-137. Abstract
  • Rahnert, J., Fan, X., Murphy, T.C., Case, N., Grassi, F., Nanes, M.S., and Rubin, J. (2008) A role for nitric oxide in the mechanical regulation of RANKL in bone stromal cells. Bone 43: 48-54. Abstract
  • Rubin, J., et al. (2007) Caveolin-1 knockout mice have increased bone size and stiffness. J Bone Mineral Res 22: 1408-18. Article [pdf]
  • Rubin, J., Murphy, T.C., Rahnert, J., Nanes, M., Greenfield, E., Jo, H., and Fan, X. (2006) Mechanical inhibition of RANKL expression requires activation of H-Ras×GTPase in a lipid raft dependent manner. J Biol Chem 281: 1412-8. Article [pdf]
  • Rubin, J., Rubin, C. and Jacobs, C. (2006) Molecular pathways of mechanical signaling in bone. Gene, 367: 1-16. Article [pdf]

Contact Information


Office Location:
5030 Burnette-Womack

Mailing Address:
CB # 7170
UNC-CH School of Medicine
Chapel Hill, NC 27599-7170

Office Phone: 919-966-6744
Lab Phone: 919-966-6743
jrubin[at]med.unc.edu

 

 

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