Paul Odgren, Ph.D.

Academic Role: Research Associate Professor

Faculty Appointment(s) In:
   Cell Biology

Bone and Cartilage Cell Biology

Deeper knowledge of basic skeletal cell biology has long-range implications for understanding many pervasive clinical conditions, such as osteoporosis, osteoarthritis, and genetic conditions that affect bone growth. Our lab group studies how the cells of the skeleton function and how they communicate and regulate one another. 

One area of focus is on evolution’s solution to a challenging problem: how can bones, which are rigid and incapable of interstitial growth, increase their size while providing skeletal support to a growing animal? For most of the skeleton, the answer is by re-enacting the evolutionary transition from a cartilaginous to a bony skeleton. We focus most of our research on mutations in rats and mice (naturally-occurring, knock-outs, and knock-ins) that block bone resorption to identify genes and signaling pathways required for normal cell differentiation and for the complex interactions of bone, cartilage, blood vessels, and marrow that control the transition from cartilage to bone during growth. We have identified genes that impact several of the constituent tissues simultaneously, pointing the way to common regulatory pathways. We bring a range of histopathologic, genetic, and molecular techniques to study these questions, including digital imaging, microarray expression profiling, cell and tissue culture, and in situ hybridization.

We are actively engaged in many collaborations with scientists in laboratories from around North America and in Europe.

Our lab continues the work of Sandy C. Marks, Jr., DDS, PhD, for more on Sandy, follow this link:
 http://www.umassmed.edu/cellbio/sandymarks.aspx

Download a memorial booklet comprised of contributions from colleagues, and friends worldwide. (PDF 2.3 MB)

Recent Publications:

B. Perdu, P. R. Odgren, L. Van Wesenbeeck, K. Jennes, C. A. MacKay, W. Van Hul. 2009. Refined genomic localization of the genetic lesion in the osteopetrosis (op) rat and exclusion of three positional and functional candidate genes, Clcn7, Atp6v0c, and Slc9a3r2. Calcified Tissue International. e-published ahead of print.

Yang, M, Birnbaum, MJ, MacKay, CA, Mason-Savas, A, Thompson, B, Odgren, PR. 2008. Osteoclast stimulatory transmembrane protein (OC-STAMP), a novel protein that promotes osteoclast differentiation. J Cellular Physiology. 215(2):497- 505.

Battaglino, RA, Pham, L, Morse, L, Vokes, M, Sharma, A, Odgren, PR, Sasaki, H, Yang, M, Stashenko, P. 2008. NHA-oc/NHA2: a mitochondrial cation-proton antiporter selectively expressed in osteoclasts. Bone 42(1) 180-192.

Mailhot G, Yang M, Mason-Savas A, Mackay CA, Leav I, Odgren PR. 2008. BMP-5 expression increases during chondrocyte differentiation in vivo and in vitro and promotes proliferation and cartilage matrix synthesis in primary chondrocyte cultures. J Cell Physiology Jan;214(1):56-64

Arnott JA, Nuglozeh E, Rico MC, Arango-Hisijara I, Odgren PR, Safadi FF and Popoff SN. 2007. Connective Tissue Growth Factor (CTGF/CCN2) is a Downstream Mediator for TGF-beta1-Induced Extracellular Matrix Production in Osteoblasts. J Celluar Physiology. 210(3):843-52.

VanWesenbeeck, L, Odgren, PR, Coxon, FP, Frattini, A, Moens, P, Perdu, B, MacKay, CA, Van Hul, E, Timmermans, J-P, Vanhoenacker, F, Jacobs, R, Peruzzi, B, Teti, A, Helfrich, MH, Rogers, MJ, Villa, A, Van Hul, W. 2007. PLEKHM1 is involved in osteoclastic vesicular transport and mutations cause osteopetrosis in the incisors absent rat and human. J Clinical Investigation 177(4):919-930.

Yang, M, MacKay, CA, Mason-Savas, A, Aubin, J, Odgren, PR. 2006. Chemokine and chemokine receptor gene expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for CCL9 (MIP-1γ) in osteoclastogenesis in vivo and in vitro. Blood 107(6):2262-2270.

Yang, M, Mailhot, G, Birnbaum, MJ, MacKay, CA, Mason-Savas, A, Odgren, PR. 2006. Expression and requirement for ovarian cancer G-protein coupled receptor 1 (OGR1) in osteoclast differentiation. Journal of Biological Chemistry, 281: 23598-23605

Odgren PR, MacKay, CA, Mason-Savas, A, Yang, M, Mailhot, G, Birnbaum, MJ. 2006. False-positive β-galactosidase staining in osteoclasts by endogenous enzyme: studies in neonatal and month-old wild type mice. Connective Tissue Research, 47(4):229-34.

Kim, N, Kadono, Y, Takami, M, Lee, J, Lee, S-H, Okada, F, Kim, JH, Kobayashi, T, Odgren, PR, Nakano, H, Ware, C, Yeh, W-C, Lee, S-K, Lorenzo, JA, Choi, Y. 2005. Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis. Journal of Experimental Medicine.202(5):589-95.

Wise, GE, S Yao, PR Odgren, F Pan. 2005. CSF-1 Regulation of Osteoclastogenesis for Tooth Eruption. Journal of Dental Research. 84(9):837-4 .

Gartland, A, Mechler J, Mason-Savas, A, MacKay, CA, Mailhot, G, Marks, SC, Jr., Odgren PR. 2005. In vitro chondrocyte differentiation using costochondral chondrocytes as a source of primary rat chondrocyte cultures: An improved isolation and cryo-preservation method. Bone, 37(4):530-44.

Yang, M, Odgren, PR. 2005. Molecular cloning and characterization of rat CCL9 (MIP-1ã), the ortholog of mouse CCL9. Cytokine. 31(2):94-102 .

Odgren, PR, A Gartland, A Mason-Savas, SC Marks, Jr. 2004. “Bone Structure,” in Encyclopedia of Endocrine Diseases, L Martini, ed. Vol. 1:392-400. Academic Press, San Diego.

Marks, SC, Jr., A Gartland, PR Odgren. 2004. “Skeletal Development” in Encyclopedia of Endocrine Diseases, L Martini, ed. Vol 4:261-272. Academic Press, San Diego.

Devraj, K, Bonassar, LJ, MacKay, CA, Mason-Savas, A, Marks, SC, Jr, Odgren, PR. Histomorphometric analysis of the growth plate chondrodysplasia in the toothless (Csf1^null) osteopetrotic rat. 2004. Connective Tissue Research 45:1-10.

Van Wesenbeeck, L, Odgren, PR, MacKay, CA, Van Hul, W. 2004. Localization of the gene causing the osteopetrotic phenotype in the incisors absent (ia) rat to chromosome 10q32.1. Journal of Bone and Mineral Research 19 (2):183-189

Odgren, PR, Philbrick, WM, Gartland, A. 2003. Perspective. Osteoclastogenesis and growth plate chondrocyte differentiation: Emergence of convergence. Critical Reviews in Eukaryotic Gene Expression. 13(2-4):181-193.

Safadi, FF, J Xu, SL Smock, RA Kanaan, A-H Selim, PR Odgren, SC Marks, Jr., TA Owen, SN Popoff. 2003. Expression of CTGF in bone: Its role in osteoblast differentiation in vitro and bone formation in vivo. Journal of Cellular Physiology 196(1):51-62.

Odgren, PR, Kim, N, MacKay, CA, Mason-Savas, A, Marks, SC Jr, Choi, Y. 2003. The role of RANKL (TRANCE), a tumor necrosis factor family member, in skeletal development: effects of gene knockout and transgenic rescue. Connective Tissue Research 44(suppl 1):264-271.

Van Wesenbeeck, L., Odgren, P. R., MacKay, C. A., D'Angelo, M., Safadi, F. F., Popoff, S. N., Van Hul, W., and Marks, S. C., Jr. (2002). The osteopetrotic mutation toothless (tl) is a loss-of-function frameshift mutation in the rat Csf1 gene: Evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification. Proc Natl Acad Sci U S A 99, 14303-14308.

Marks, S. C., Jr., and Odgren, P. R. (2002). The structure and development of the skeleton. In Principles of Bone Biology, J. P. Bilezikian, L. G. Raisz and G. A. Rodan, eds. (New York: Academic Press), pp. 3-15.

Odgren, P. R., Kim, N., Van Wesenbeeck, L., MacKay, C. A., Mason-Savas, A., Safadi, F. F., Popoff, S. N., Lengner, C., Van Hul, W., Choi, Y., and Marks, S. C. J. (2001). Evidence that the rat osteopetrotic mutation toothless (tl) is not in the TNFSF11 (TRANCE, RANKL, ODF, OPGL) gene. Int J Devel Biol 45, 853-859.

Kim, N., Odgren, P. R., Kim, D. K., Marks, S. C., Jr., and Choi, Y. (2000). Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene. Proc Natl Acad Sci U S A 97, 10905-10910.

Xu, J., Smock, S. L., Safadi, F. F., Rosenzweig, A. B., Odgren, P. R., Marks, S. C., Jr., Owen, T. A., and Popoff, S. N. (2000). Cloning the full-length cDNA for rat connective tissue growth factor: implications for skeletal development. J Cell Biochem 77, 103-15.

Marks, S. C., Jr., Lundmark, C., Wurtz, T., Odgren, P. R., MacKay, C. A., Mason-Savas, A., and Popoff, S. N. (1999). Facial development and type III collagen RNA expression: concurrent repression in the osteopetrotic (Toothless, tl) rat and rescue after treatment with colony-stimulating factor-1. Dev Dyn 215, 117-25.

Odgren, P. R., Popoff, S. N., Safadi, F. F., MacKay, C. A., Mason-Savas, A., Seifert, M. F., and Marks, S. C., Jr. (1999). The toothless osteopetrotic rat has a normal vitamin D-binding protein-macrophage activating factor (DBP-MAF) cascade and chondrodysplasia resistant to treatments with colony stimulating factor-1 (CSF-1) and/or DBP-MAF. Bone 25, 175-81.

Potential Rotation Projects

Specific projects will depend on student interests and previous lab experience, but could include digital microscopy, tissue preparation and staining, in situ hybridization, northern and/or western blots, PCR, and in vitro transcription. Specifically, riboprobe synthesis from cDNA clones and their use for in situ hybridization studies of gene expression skeletal tissues; Northern and Western blots to follow gene expression both in tissues and in cells differentiated in culture; developing and applying immunohistology methods to detect specific proteins in skeletal tissues; treating animals with growth factors or cytokines to follow the impact on the skeleton and other tissues.

Students are encouraged to work on projects of sufficient focus that they are likely to be completed during the rotation period.

Biography

Ph.D. UMass Medical School, 1995
B.S. UMass Amherst, 1989

Office: S7-242
Phone: 508-856-8609
E-mail: Paul.Odgren@umassmed.edu
Keywords: Cell Biology, Gene Expression

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