title: The expression of IL-6 by osteoblasts is increased in healthy elderly individuals: stimulated proliferation and differentiation are unaffected by age.
abstract: Increasing age is associated with reduced bone mineral content and increased risk of fractures. This is caused by a relative insufficiency of osteoblasts compared with osteoclasts. We therefore wanted to examine the potential differences in proliferation, differentiation, and expression of cytokines between human osteoblasts (hOBs) obtained from young and elderly individuals. Cultures of hOBs were obtained from 11 elderly (73-85 years) and 15 young (21-27 years) healthy individuals. The cells were stimulated with hGH, IGF-I, hGH + IGF-I, and TGF-β1. Proliferation was evaluated by thymidine incorporation, and differentiation was evaluated by alkaline phosphatase, OPG, and PINP production. Expression of IL-6, TGF-β1, OPG, and RANKL was investigated using real-time PCR and three carefully selected housekeeping genes. Combined stimulation with hGH and IGF-I increased proliferation without differences between hOBs obtained from young and elderly individuals. hOBs from young individuals responded to stimulation with vitamin D with a more pronounced increase in alkaline phosphatase: 107 ± 17% vs. 43 ± 5%, P < 0.01. Stimulation with TGF-β1 decreased OPG production by hOBs from elderly individuals but not from young individuals, P < 0.05. hOBs from elderly individuals expressed significantly higher amounts of IL-6 mRNA (P < 0.05) and less OPG and TGF-β1 mRNA (P = 0.08 and P = 0.08, respectively) compared with hOBs from young individuals. In conclusion, hOBs from elderly individuals express more IL-6 mRNA and less OPG and TGF-β1 mRNA than hOBs from young individuals. This could partly explain the reduced bone mass and increased fracture risk seen in the elderly. hOBs from young and elderly individuals responded similarly to short-term stimulation of proliferation and differentiation.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000, Aarhus C, Denmark.
authors.forename: Charlotte Grith
authors.initials: CG
authors.lastname: Eriksen
authors.forename: Helene
authors.initials: H
authors.lastname: Olsen
authors.forename: Lise Bjerre
authors.initials: LB
authors.lastname: Husted
authors.forename: Lotte
authors.initials: L
authors.lastname: Sørensen
authors.forename: Mette
authors.initials: M
authors.lastname: Carstens
authors.forename: Kjeld
authors.initials: K
authors.lastname: Søballe
authors.forename: Bente Lomholt
authors.initials: BL
authors.lastname: Langdahl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001861:Bone Regeneration / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D010006:Osteoblasts / Q000473:pathology / Q000502:physiology*; D010024:Osteoporosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D053244:Osteoprotegerin; D012333:RNA, Messenger