Histone Deacetylases in Bone Development and Bone Diseases
Microcomputed tomography reconstructions of cortical bone (left), cancellous bone (middle) and bone marrow fat (yellow, right) in Hdac3-depleted mice. Credit: Meghan McGee-Lawrence, Ph.D., Dana L. Begun, Ph.D.
Dr. Westendorf's Skeletal Development and Regeneration Research Laboratory is studying histone deacetylases in bone development and bone diseases.
This project in Dr. Westendorf's lab is designed to determine how Hdacs and associated epigenetic factors control bone development and disease. This work is clinically significant because Hdac inhibitors and other epigenetic drugs are entering the clinic at rapid rates for the treatment of cancer and many other conditions.
Mayo Clinic collaborators: Elizabeth W. Bradley, Ph.D., and Andre J. van Wijnen, Ph.D.
- Schroeder TM, Kahler RA, Li X, Westendorf JJ. Histone deacetylase 3 interacts with Runx2 to repress the osteocalcin promoter and regulate osteoblast differentiation. J Biol Chem. 2004; 279: 41998-2007.
- Dudakovic A, Evans JM, Li Y, Middha S, McGee-Lawrence ME, van Wijnen AJ, Westendorf JJ. Histone deacetylase inhibition promotes osteoblast maturation by altering the histone H4 epigenome and reduces Akt phosphorylation. J Biol Chem. 2013; 288(40): 28783-91.
- McGee-Lawrence ME, McCleary-Wheeler AL, Secreto FJ, Razidlo DF, Zhang M, Stensgard BA, Li X, Stein GS, Lian JB, Westendorf JJ. Suberoylanilide hydroxamic acid (SAHA; vorinostat) causes bone loss by inhibiting immature osteoblasts. Bone. 2011; 48: 1117-26.
- Razidlo DF, Whitney TJ, Casper ME, McGee-Lawrence ME, Stensgard BA, Secreto FJ, Li X, Knutson SK, Hiebert SW, Westendorf JJ. Histone deacetylase 3 depletion in osteo/chondro-progenitor cells decreases bone density and increases marrow fat. PLoS ONE. 2010; 5(7): e11492.
- McGee-Lawrence ME, Bradley EW, Dudakovic A, Carlson SW, Ryan ZC, Kumar R, Dadsetan M, Yaszemski MJ, Chen Q, An KN, Westendorf JJ. Histone deacetylase 3 is required for maintenance of bone mass during aging. Bone. 2013; 52: 296-307.
- McGee-Lawrence ME, Carpio LR, Schulze RJ, Pierce JL, McNiven MA, Farr JN, Khosla S, Oursler MJ, Westendorf JJ. Hdac3 deficiency increases marrow adiposity and induces lipid storage and glucocorticoid metabolism in osteochondroprogenitor cells. J Bone Miner Res. 2016; 31:116-28.
- Carpio LR, Bradley EW, McGee-Lawrence ME, Weivoda MM, Poston DD, Dudakovic A, Xu M, Tchkonia T, Kirkland JL, van Wijnen AJ, Oursler MJ, Westendorf JJ. Histone deacetylase 3 supports endochondral bone formation by controlling cytokine signaling and matrix remodeling. Sci Signal. 2016; 9(440): ra79.