The Expression of IL-6 by Osteoblasts Is Increased in Healthy Elderly Individuals: Stimulated Proliferation and Differentiation Are Unaffected by Age

被引:10
作者
Eriksen, Charlotte Grith [1 ,2 ]
Olsen, Helene [1 ,2 ]
Husted, Lise Bjerre [1 ]
Sorensen, Lotte [1 ]
Carstens, Mette [1 ]
Soballe, Kjeld [2 ]
Langdahl, Bente Lomholt [1 ]
机构
[1] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus C, Denmark
[2] Aarhus Univ Hosp, Dept Orthoped Surg, DK-8000 Aarhus C, Denmark
关键词
Osteoblast; Interleukin-6; Transforming growth factor-beta 1; Age; OPG; RANKL; GROWTH-FACTOR-BETA; OSTEOCLASTOGENESIS-INHIBITORY FACTOR; MARROW STROMAL CELLS; OSTEOPROTEGERIN MESSENGER-RNA; POLYMERASE CHAIN-REACTION; KAPPA-B LIGAND; HUMAN BONE; IN-VITRO; POSTMENOPAUSAL OSTEOPOROSIS; GENE-EXPRESSION;
D O I
10.1007/s00223-010-9412-x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-beta 1. Proliferation was evaluated by thymidine incorporation, and differentiation was evaluated by alkaline phosphatase, OPG, and PINP production. Expression of IL-6, TGF-beta 1, 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 +/- A 17% vs. 43 +/- A 5%, P < 0.01. Stimulation with TGF-beta 1 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-beta 1 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-beta 1 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.
引用
收藏
页码:414 / 423
页数:10
相关论文
共 60 条
[1]   Inhibition of osteoblast differentiation but not adipocyte differentiation of mesenchymal stem cells by sera obtained from aged females [J].
Abdallah, Basem M. ;
Haack-Sorensen, Mandana ;
Fink, Trine ;
Kassem, Moustapha .
BONE, 2006, 39 (01) :181-188
[2]   Increased RANKL/OPG mRNA ratio in iliac bone biopsies from women with hip fractures [J].
Abdallah, BM ;
Stilgren, LS ;
Nissen, N ;
Kassem, M ;
Jorgensen, HRI ;
Abrahamsen, B .
CALCIFIED TISSUE INTERNATIONAL, 2005, 76 (02) :90-97
[3]   Cytokines and bone loss in a 5-year longitudinal study - Hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: The Danish Osteoporosis Prevention Study [J].
Abrahamsen, B ;
Bonnevie-Nielsen, V ;
Ebbesen, EN ;
Gram, J ;
Beck-Nielsen, H .
JOURNAL OF BONE AND MINERAL RESEARCH, 2000, 15 (08) :1545-1554
[4]   Osteoclastogenesis inhibitory factor suppresses osteoclast survival by intetfering in the interaction of stromal cells with osteoclast [J].
Akatsu, T ;
Murakami, T ;
Nishikawa, M ;
Ono, K ;
Shinomiya, N ;
Tsuda, E ;
Mochizuki, S ;
Yamaguchi, K ;
Kinosaki, M ;
Higashio, K ;
Yamamoto, M ;
Motoyoshi, K ;
Nagata, N .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 250 (02) :229-234
[5]   Different gene expression patterns in the bone tissue of aging postmenopausal osteoporotic and non-osteoporotic women [J].
Balla, Bernadett ;
Kosa, Janos P. ;
Kiss, Janos ;
Borsy, Adrienn ;
Podani, Janos ;
Takacs, Istvan ;
Lazary, Aron ;
Nagy, Zsolt ;
Bacsi, Krisztian ;
Speer, Gabor ;
Orosz, Laszlo ;
Lakatos, Peter .
CALCIFIED TISSUE INTERNATIONAL, 2008, 82 (01) :12-26
[6]   Activation of the Janus kinase/STAT (signal transducer and activator of transcription) signal transduction pathway by interleukin-6-type cytokines promotes osteoblast differentiation [J].
Bellido, T ;
Borba, VZC ;
Roberson, P ;
Manolagas, SC .
ENDOCRINOLOGY, 1997, 138 (09) :3666-3676
[7]  
BONEWALD LF, 1990, CLIN ORTHOP RELAT R, P261
[8]   Regulation and regulatory activities of transforming growth factor β [J].
Bonewald, LF .
CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION, 1999, 9 (01) :33-44
[9]   Tumor necrosis factor-α and -β upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells [J].
Brändström, H ;
Jonsson, KB ;
Vidal, O ;
Ljunghall, S ;
Ohlsson, C ;
Ljunggren, Ö .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 248 (03) :454-457
[10]   Expression and function of TNF-family proteins and receptors in human osteoblasts [J].
Bu, RF ;
Borysenko, CW ;
Li, YN ;
Cao, LH ;
Sabokbar, A ;
Blair, HC .
BONE, 2003, 33 (05) :760-770