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Dr. Kronenberg’s laboratory uses genetically manipulated mice to study signaling by the PTH/PTHrP receptor, bone development and the regulation of hematopoiesis by cells of the osteoblast lineage. We meet regularly with members of Cliff Tabin’s group to discuss bone-development projects and with David Scadden’s group to discuss projects involving the fates of cells of the osteoblast lineage and the interactions of these cells with hematopoietic cells.
Visit the Harvard Catalyst website to see a full list of Dr. Kronenberg’s publications
Current projects include:
1. Origin of osteoblasts in the primary spongiosa. Christa Maes used a lineage-tracing strategy to mark a subset of periosteal cells early in bone development that express the osterix gene. By following the fates of these cells, she showed that they and their descendants populate the primary spongiosa. After such cells begin expressing the collagen I(aI) promoter in the perichondrium, they can no longer contribute to the primary spongiosa. Noriaki Ono then used the collagen II and S0X9 promoters--promoters aactive in mesenchymal condensations--to mark growth-associated stem cells in bone, and showed that these cells, over time, generate osteoblasts, stromal cells, adipocytes and chondrocytes.
2. Shigeki Nishimori is using mutant mice to establish the hypothesis that PTHrP slows chondrocyte differentiation by leading to the dephosphorylation of HDAC4 and 5 and causing their movement into the nucleus, causing inhabition of the actions of MEF2c and Runx2.
3. Marc Wein, in collaboration with Dr. Divieti Pajevic, is examining the pathways by which PTH suppresses sclerostin expression in the osteocyte cell line. He has shown that activation of protein kinase A leads to a cascade the eventuates in the inhibition of Mef2c action by HDACs 4 and 5, leading to suppression of sclerostin gene expression.
4. Hong Mei, in collaboration with David Scadden, has begun to examine the origins of cells that repair injured articular cartilage.
5. Deepak Balani is studying the role of parathyroid hormone (PTH) in activating early cells of the osteoblast lineage. He is using genetically marked mice to identify these cells and study PTH action in vivo.
6. Tetsuya Enishi, with Marc Wein, is identifying the mechanisms used by PTH and by anti-sclerostin antibody to activate dormant bone lining cells.
Henry Kronenberg, MD
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