Aberrant gene expression profiles, during in vitro osteoblast differentiation, of telomerase deficient mouse bone marrow stromal stem cells (mBMSCs)

Journal of Biomedical Science

Mehwish Iqtedar²  Hamid Saeed¹ 

[1]University College of Pharmacy, Punjab University, Allama Iqbal Campus, Lahore, 54000, Pakistan

[2]Department of Bio-technology & Microbiology, Lahore College for Women University, Lahore, Pakistan

关键词: Osteoblast;    Aging;    Mesenchymal stem cells;    BMSCs;    Telomeres;    Telomerase;   

Others  :  1133558
DOI  :  10.1186/s12929-015-0116-4

 received in 2014-06-13, accepted in 2015-01-21,  发布年份 2015

【 摘 要 】

Background

Telomerase deficiency has been associated with inadequate differentiation of mesenchymal stem cells. However, the effect of telomerase deficiency on differential regulation of osteoblast specific genes, based on functional gene grouping, during in vitro osteoblast differentiation has not been reported before.

Results

To examine these effects, Terc^-/- BMSCs (bone marrow stromal stem cells) were employed which exhibited reduced proliferation during in vitro osteogenesis along with increased population doubling time and level compared to wild type (WT) BMSCs during the normal culture. Osteogenic super array at day 10 of osteoblast differentiation revealed that telomerase deficiency strongly affected the osteoblast commitment by down-regulating Runx2, Twist and Vdr – known transcription regulators of osteogenesis. Similarly, in Terc^-/- BMSCs a marked reduction in other genes engaged in various phases of osteoblast differentiation were observed, such as Fgfr2 involved in bone mineralization, Phex and Dmp1 engaged in ossification, and Col11a1 and Col2a1 involved in cartilage condensation. A similar trend was observed for genes involved in osteoblast proliferation (Tgfb1, Fgfr2 and Pdgfa) and bone mineral metabolism (Col1a1, Col2a1, Col1a2 and Col11a1). More profound changes were observed in genes engaged in extracellular matrix production: Col1a1, Col1a2, Mmp10, Serpinh1 and Col4a1.

Conclusion

Taken together, these data suggest that telomerase deficiency causes impairment of BMSCs differentiation into osteoblasts affecting commitment, proliferation, matrix mineralization and maturation. Thus, modulating telomerase in BMSCs with advanced aging could improve BMSCs responsiveness towards osteoblast differentiation signals, optimal for osteoblast commitment, proliferation and maturation processes.

【 授权许可】

   
2015 Saeed and Iqtedar; licensee BioMed Central.

【 图 表 】

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