Effects of age on parathyroid hormone signaling in human marrow stromal cells
| Autor: | Ilan Bleiberg, Sung Won Kim, Julie Glowacki, Paul Morley, Jochen Hahne, Longxiang Shen, Shuanhu Zhou, Ilaria Amato, Ericka M. Bueno |
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| Rok vydání: | 2011 |
| Předmět: |
endocrine system
Aging medicine.medical_specialty Stromal cell biology Parathyroid hormone Stimulation Osteoblast Cell Biology equipment and supplies CREB Endocrinology medicine.anatomical_structure Downregulation and upregulation Internal medicine medicine biology.protein Alkaline phosphatase hormones hormone substitutes and hormone antagonists Dexamethasone medicine.drug |
| Zdroj: | Aging Cell. 10:780-788 |
| ISSN: | 1474-9718 |
| Popis: | Summary Human bone marrow stromal cells (hMSCs) have the potential to differentiate into osteoblasts; there are age-related decreases in their proliferation and differentiation to osteoblasts. Parathyroid hormone (PTH), when applied intermittently in vivo, has osteoanabolic effects in a variety of systems. In this study, we compared PTH signaling and osteoanabolic effects in hMSCs from young and old subjects. There were age-related decreases in expression of PTH/PTHrP receptor type 1 (PTHR1) gene (P = 0.049, n = 19) and in PTH activation of CREB (P = 0.029, n = 7) and PTH stabilization of β-catenin (P = 0.018, n = 7). Three human PTH peptides, PTH1-34, PTH1-31C (Ostabolin-C, Leu27, Cyclo[Glu22-Lys26]-hPTH1-31), and PTH1-84 (10 nm), stimulated osteoblast differentiation with hMSCs. Treatment with PTH1-34 resulted in a significant 67% increase in alkaline phosphatase activity in hMSCs obtained from younger subjects ( 55 years old, n = 7). Both knockdown of CREB and treatment with a protein kinase A inhibitor H-89 blocked PTH stimulation of osteoblast differentiation in hMSCs from young subjects. The PTH peptides significantly stimulated proliferation of hMSCs. Treatment with PTH1-34 resulted in an average of twice as many cells in cultures of hMSCs from young subjects (n = 4), but had no effect with hMSCs from elders (n = 7). Upregulation of PTHR1 by 24-h pretreatment with 100 nm dexamethasone rescued PTH stimulation of proliferation in hMSCS from elders. In conclusion, age-related intrinsic alterations in signaling responses to osteoanabolic agents like PTH may contribute to cellular and tissue aging of the human skeleton. |
| Databáze: | OpenAIRE |
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