Bone marrow mesenchymal stem cells have the potential to differentiate to lineages of mesenchymal tissues, including osteoblasts, adipocytes, chondrocytes, fibroblasts and myoblasts. Dr. Cao studies the microenvironment that is necessary for differentiation of the multipotential stem cells into functionally distinct cell types such as osteoblasts. Parathyroid hormone and TGFß1 are the important factors that regulate the fate of mesenchymal stem cells. The primary goal of Dr. Cao’s research is to study the role of bone marrow mesenchymal stem cells in bone remodeling, osteoporosis and osteoarthritis.
The Cao lab studies the regulation of bone marrow mesenchymal stem cell lineage commitment. Dr. Cao and his research team found that TGFß1 induces mesenchymal stem cell migration to couple bone resorption and formation during bone remodeling. High levels of active TGFß1 in the bone marrow microenvironment change the fate of mesenchymal stem cells and lead to skeletal disorders such as osteoarthritis. The team is characterizing the markers of mesenchymal stem cells through lineage tracing and determining their role in bone remodeling. In parallel, studies are underway to develop therapies for osteoarthritis by modulating mesenchymal stem cells.
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Bianco P, Cao X, Frenette PS, Mao JJ, Robey PG, Simmons PJ, Wang CY. "The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine." Nat Med. 2013 Jan;19(1):35-42. doi: 10.1038/nm.3028. Epub 2013 Jan 7.
Wan M, Li C, Zhen G, Jiao K, He H, Jia X, Wang W, Shi C, Xing X, Chen Y, Jan De Beur S, Yu B, Cao X. "Injury-activated TGFB controls mobilization of MSCs for tissue remodeling." Stem Cell. 2012;30(11):2498-511. doi: 10.1002.
Xian L, Lou M, Wu X, Yu B, Frassica F, Wan M, Pang L, Wen C, Tryggestad E, Wong J, Cao X. "Pretreatment with antioxidants prevent bone injury by improving bone marrow microenvironment for stem cells." Stem Cell Discovery. 2012;2:100-107. doi: 10.4236/scd.2012.23015.
Yu B, Zhao X, Yang C, Xian L, Lu W, Wan M, Cao X. "PTH induces differentiation of mesenchymal stem cells by activation of BMP signaling." JBMR. 2012;27(9):2001-14. doi: 10.1002/jbmr.1663.
Xian L, Wu X, Pang L, Lou M, Rosen C, Qiu T, Crane J, Frassica F, Zhang L, Rodriguez JP, Jia X, Yakar S, Xuan S, Efstratiadis A, Wan M, Cao X. "Matrix IGF-1 regulates bone mass by activation of mTOR in mesenchymal stem cells." Nat Med. 2012;18(7):1095-101.