Yale Core Center for Musculoskeletal Disorders
Interactions between the skeletal, immune, and hematopoietic systems as they relate to normal and pathologic bone remodeling. Transgenic mice are used to investigate osteoblast and osteoclast development.
Extensive Research Description
The laboratory is focused on two areas. The first, is osteoimmunology and the second is the relationship of adipose tissue to bone. To this end we are examining a number of transgenic animal models many of which have specific transcription factors deleted, one result being bone alterations. As an example the loss of GATA-1, a transcription factor required for megakaryocyte differentiation, have a phenotype characterized by an increase in the number of megakaryocytes, no functional platelets and a massive increase in both trabecular and cortical bone. We are in the process of characterizing both the bone phenotype and the underlying mechanism responsible for the increased bone mass. In addition, we are looking at mice deficient in transcription factors required for B cell differentiation. Ebf1 deficient mice lack B cells but also have increased bone formation and increased marrow fat. Increased fat usually occurs at the expense of osteoblastogenesis. Because of the lipodystrophic phenotype of Ebf1 deficient mice, we are developing models for increased marrow fat. Marrow fat increases with age. However, is function as well as its origin are unknown. In a separate project, we are isolating cells from inside, rather than on bone surfaces. These cells are heterogeneous and have some characteristics of osteocytes.
- Analysis of the bone and fat phenotype of mice lacking the B cell transcription factors Ebf1 and Pax5
- Analysis of the bone phenotype of mice lacking GATA1
- Isolation and characterization of bone cells from inside bone (osteocytes).
- Develop mouse models for marrow fat.
- Hesslein DG, Fretz JA, Xi Y, Nelson T, Zhou S, Lorenzo JA, Schatz DG, Horowitz MC. Ebf1-dependent control of the osteoblast and adipocyte lineages. Bone. 2009 Apr;44(4):537-46. Epub 2008 Dec 16.
- Ciovacco WA, Goldberg CG, Taylor AF, Lemieux JM, Horowitz MC, Donahue HJ, Kacena MA. The role of gap junctions in megakaryocyte-mediated osteoblast proliferation and differentiation. Bone. 2009 Jan;44(1):80-6. Epub 2008 Sep 10.