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Additive effects of estrogen and mechanical stress on nitric oxide and prostaglandin E2 production by bone cells from osteoporotic donors

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Abstract

Mechanical loading is thought to provoke a cellular response via loading-induced flow of interstitial fluid through the lacuno-canalicular network of osteocytes. This response supposedly leads to an adaptation of local bone mass and architecture. It has been suggested that loss of estrogen during menopause alters the sensitivity of bone tissue to mechanical load, thereby contributing to the rapid loss of bone. The present study aimed to determine whether estrogen modulates the mechanoresponsiveness of bone cells from osteoporotic women. Bone cell cultures from nine osteoporotic women (aged 62–90 years) were pre-cultured for 24 h with 10−11 mol/l 17β-estradiol (E2) or vehicle, and subjected to 1 h of pulsating fluid flow (PFF) or static culture. E2 alone enhanced prostaglandin E2 (PGE2) and nitric oxide (NO) production by 2.8-fold and 2.0-fold, respectively, and stimulated endothelial nitric oxide synthase protein expression by 2.5-fold. PFF, in the absence of E2, stimulated PGE2 production by 3.1-fold and NO production by 3.9-fold. Combined treatment with E2 and PFF increased PGE2 and NO production in an additive manner. When expressed as PFF-treatment-over-control ratio, the response to fluid shear stress was similar in the absence or presence of E2. These results suggest that E2 does not affect the early response to stress in bone cells. Rather, E2 and shear stress both promote the production of paracrine factors such as NO and PGE2 in an additive manner.

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Acknowledgments

The authors thank C.M. Semeins and H.F. Teshale for their expert technical assistance. We thank Drs P. Patka, A. van Kampen, E. Hoebink and T. Patt for their assistance in obtaining osteoporotic bone material, M.N. Helder for kindly providing PCR-primers for cbfa1, and M. Joldersma for providing the raw data of her study on osteoarthritic women. The Netherlands Organization for Scientific Research supported the work of A.D. Bakker (NWO Grant 903-41-193) who also received a financial contribution from the Stichting Anna Fonds. The European Community supported the work of J. Klein-Nulend (fifth framework grant QLK3-1999-00559).

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Authors and Affiliations

  1. Department of Oral Cell Biology, ACTA-UvA and Vrije Universiteit, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands

    A. D. Bakker, J. Klein-Nulend & E. H. Burger

  2. Orthopedic Research Laboratory, UMC Nijmegen, Nijmegen, The Netherlands

    E. Tanck

  3. Department of Orthopedics, Hilversum Hospital, Hilversum, The Netherlands

    G. H. Albers

  4. Department of Endocrinology, VU-University Medical Center, Amsterdam, The Netherlands

    P. Lips

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  1. A. D. Bakker
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  2. J. Klein-Nulend
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  3. E. Tanck
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  4. G. H. Albers
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  5. P. Lips
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  6. E. H. Burger
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Correspondence to J. Klein-Nulend.

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Bakker, A.D., Klein-Nulend, J., Tanck, E. et al. Additive effects of estrogen and mechanical stress on nitric oxide and prostaglandin E2 production by bone cells from osteoporotic donors. Osteoporos Int 16, 983–989 (2005). https://doi.org/10.1007/s00198-004-1785-0

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  • DOI: https://doi.org/10.1007/s00198-004-1785-0

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