Mitogenic responsiveness of human bone cells in vitro to hormones and growth factors decreases with age

Abstract

Bone loss with aging may at least in part be due to inadequate bone formation. In this study, we examined whether the proliferation of osteoblast-like cells in vitro in response to local and systemic factors might be attenuated with age. A total of 36 cultures of osteoblast-like cells were obtained from outgrowths of human trabecular bone. Parathyroid hormone, growth hormone, calcitonin, transforming growth factor beta, insulin-like growth factor I, and platelet-derived growth factor BB dose dependently increased DNA synthesis in all cultures. Increases in DNA synthesis with each of these factors were significantly negatively correlated with donor age in cultures obtained from the iliac crest bone of 50- to 70-year-old women. Cells from 61- to 70-year-old donors required approximately 10-fold higher concentrations of growth factors and hormones to yield comparable increases in DNA synthesis than cells from 51- to 60-year-old donors. A significant negative correlation between age and mitogenic responsiveness to platelet-derived growth factor and growth hormone, but not toward the other factors, was also observed in cultures from the femoral head trabecular bone of 60- to 90-year-old women. Our findings suggest that bone loss with aging may be partially due to a decreased capacity of osteoblasts to proliferate in response to systemic or locally released osteotropic factors.

Activated platelets increase fibrinolysis of mesenchymal progenitor cells

“…With increasing age of the donor, however, mesenchymal progenitor cells are not substantially diminished in their responsiveness to signaling molecules, likely because they maintain their stem-cell characteristics. 48,49 In conclusion, the present report demonstrates that activated platelets increase uPA dependent plasminogen activation in mesenchymal progenitors involving JNK and PI3K/AKT signaling. These in vitro findings may add to our understanding of the cellular mechanisms by which platelets contribute to the organization of the blood clot during bone regeneration.…”

The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis

“…Bone responsiveness to IGF1 also decreases with aging (Kveiborg et al 2000). The skeletal anabolic response to IGF1 administration is weakened in the elderly, and biopsy-derived osteoblasts from patients of different ages respond to IGF1 by increasing proliferation, but the dose needed to elicit a response is an order of magnitude greater for cells from aged patients (Pfeilschifter et al 1993). These studies suggest that low circulating IGF1 bioactivity and abnormalities of IGF1 signaling in elderly subjects, especially in those individuals with an age-related proinflammatory state (i.e.…”

Senescence‐associated intrinsic mechanisms of osteoblast dysfunctions

“…In mice, aging has been reported to cause decrease in insulin-like growth factor (IGF)-I effects on osteoblast proliferation and differentiation owing to defective IGF-1 signaling (Cao et al, 2007). In humans, osteoblastic cells from aged donors exhibit decreased proliferative responses to growth hormone and platelet-derived growth factor compared with young donor cells (Pfeilschifter et al, 1993). Similarly, osteoblast cultures obtained from young subjects exhibited a better response to estradiol (Ankrom et al, 1998) and IGF-I (D'Avis et al, 1997) compared with cells obtained from older donors.…”