Investigating the possible roles of <em>HOPX, CMTM8</em> and <em>ALOX15B</em> during bone marrow mesenchymal stem cell (BMSC) proliferation and cell fate determination in postnatal bone formation — ASN Events
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  3. Investigating the possible roles of HOPX, CMTM8 and ALOX15B during bone marrow mesenchymal stem cell (BMSC) proliferation and cell fate determination in postnatal bone formation

Investigating the possible roles of HOPX, CMTM8 and ALOX15B during bone marrow mesenchymal stem cell (BMSC) proliferation and cell fate determination in postnatal bone formation (#161)

Chee Hng 1 2 , Esther Camp-Dotlic 1 2 , Peter Anderson 3 , Stan Gronthos 1 2
  1. Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
  2. Mesenchymal Stem Cell Laboratory, Cancer Theme, South Australia Health and Medical Research Institute, Adelaide, SA, Australia
  3. Adelaide Craniofacial Unit, Women and Children Hospital, North Adelaide, SA, Australia

Bone marrow-derived mesenchymal stem cells (BMSC) are self-renewing, multipotent cells that can give rise to multiple lineages including osteoblasts (bone), chondrocytes (cartilage) and adipocytes (fat). Interestingly, pathways that promote osteogenesis/chondrogenesis of BMSC simultaneously suppress pathways that induce adipogenesis and vice versa1-2.

The bHLH transcription factor, TWIST-1 is highly expressed by BMSC and plays an important role in BMSC self-renewal and differentiation3-5. However, many of the underlying mechanisms of how TWIST-1 regulates BMSC division and differentiation still remain poorly understood and as a consequence, ineffective control of BMSC lifespan and lineage commitment remains a hurdle for clinical use of BMSC.

In order to identify novel TWIST-1 gene targets involved in BMSC proliferation and osteogenic differentiation we have previously performed microarray analysis to compare the gene expression profile of BMSC which express either endogenous or enforced expression of TWIST-1 during growth culture conditions or undergoing osteogenic differentiation. A number of differentially expressed genes were identified. A few novel differentially expressed genes include HOPX, CMTM8 and ALOX15B. There is currently no known function of these genes during BMSC growth or differentiation. We aim to determine whether these genes are novel targets of TWIST-1 in BMSC and thus possibly be involved in mediating the effects of TWIST-1 on cell proliferation and lineage commitment.

To date, our study shows that there is a negative correlation of expression between TWIST-1 and these three genes during osteogenesis and adipogenesis of BMSC differentiation. In addition, functional studies suggest that HOPX, CMTM8 and ALOX15B act as negative regulators of BMSC adipogenic differentiation while positively regulating the proliferation. Current studies are investigating their roles in BMSC during osteogenesis and chondrogenesis. These studies will provide better understanding of the molecular mechanisms of TWIST-1 mediated bone formation and postnatal homeostasis and therefore lead to better control of BMSC lifespan and lineage commitment. 

  1. Beresford, J. N., et al. (1992). "Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures." J Cell Sci 102 ( Pt 2): 341-351.
  2. Gimble, J. M., et al. (1995). "Bone morphogenetic proteins inhibit adipocyte differentiation by bone marrow stromal cells." J Cell Biochem 58(3): 393-402.
  3. Menicanin, D., et al. (2010). "Identification of a common gene expression signature associated with immature clonal mesenchymal cell populations derived from bone marrow and dental tissues." Stem Cells Dev 19(10): 1501-1510.
  4. Isenmann, S., et al. (2009). "TWIST family of basic helix-loop-helix transcription factors mediate human mesenchymal stem cell growth and commitment." Stem Cells 27(10): 2457-2468.
  5. Cakouros, D., et al. (2012). "Twist-1 induces Ezh2 recruitment regulating histone methylation along the Ink4A/Arf locus in mesenchymal stem cells." Mol Cell Biol 32(8): 1433-1441.