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Published on: February 28, 2017
Telomerase activity promotes osteoblast differentiation by modulating IGF-signaling pathway
Hamid Saeed1,2, Weimin Qiu3, Chen Li4
1Molecular Endocrinology Laboratory (KMEB), Department of Endocrinology and Metabolism, Medical Biotechnology Center, Odense University Hospital & University of Southern Denmark, SDU, 5000, Odense C, Denmark. hamid.pharmacy@pu.edu.pk.
Telomere maintenance through telomerase is crucial for bone health. Impaired insulin-like growth factor (IGF) signaling due to telomerase deficiency reduces osteoblast function and bone formation.
Area of Science:
- Cell Biology
- Bone Biology
- Aging Research
Background:
- Telomerase activity's role in age-related bone decline is understudied.
- Previous work showed telomerase overexpression enhances osteoblast differentiation.
Purpose of the Study:
- Investigate signaling pathways of telomerase in osteoblastic cells.
- Elucidate telomerase's regulatory mechanisms in bone formation.
Main Methods:
- Comparative microarray and Western blot analysis of telomerase-overexpressing and primary human bone marrow skeletal stem cells (hMSC).
- Analysis of osteoblastic cells from telomerase-deficient (Terc(-/-)) mice.
- Assessment of insulin-like growth factor (IGF) signaling components and alkaline phosphatase (ALP) activity.
Main Results:
- Telomerase overexpression upregulated IGF signaling components in hMSC.
- Increased IGF-induced AKT phosphorylation and ALP activity observed in hMSC-TERT.
- Telomerase deficiency reduced IGF signaling, serum IGF1/IGFBP3, and skeletal IGF gene expression in mice.
- Impaired IGF1-induced osteoblast differentiation in Terc(-/-) MSC.
Conclusions:
- Impaired IGF/AKT signaling contributes to reduced bone mass in telomerase-deficient cells.
- Telomerase influences bone formation via the IGF signaling pathway.
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