Abstract
Introduction
Osteoporosis (OP) and osteoarthritis (OA) are both common diseases in the elderly, but remarkably seldom coexist. The bone defects that are related to both diseases develop with increasing age, which suggests that they are related to some form of imperfect bone remodeling. Current opinion holds that the bone remodeling process is supervised by bone cells that respond to mechanical stimuli. An imperfect response of bone cells to mechanical stimuli might thus relate to imperfect bone remodeling, which could eventually lead to a lack bone mass and strength, such as in OP patients.
Materials
To investigate whether the cellular response to mechanical stress differs between OP and OA patients, we compared the response of bone cells from both groups to fluid shear stress of increasing magnitude. Bone cells from 9 female OP donors (age 60-90 year) and 9 female age-matched OA donors were subjected to pulsating fluid flow (PFF) of low (0.4±0.1 Pa at 3 Hz), medium (0.6±0.3 Pa at 5 Hz), or high shear stress (1.2±0.4 at 9Hz), or were kept under static culture conditions.
Results
We found subtle differences in the shear-stress response of the two groups, measured as nitric oxide (NO) and prostaglandin E2 (PGE2) production. The NO-response to shear stress was higher in the OP than the OA cells, while the PGE2-response was higher in the OA cells.
Conclusions
Assuming that NO and PGE2 play a role in cell-cell communication during remodeling, these results suggest that slight differences in mechanotransduction might relate to the opposite bone defects in osteoporosis and osteoarthritis.
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References
Eriksen EF, Hodgson SF, Eastell R, Cedel SL, O’Fallon WM, Riggs L (1990) Cancellous bone remodeling in type I (postmenopausal) osteoporosis: quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular levels. J Bone Miner Res 5:311–319
Richelson LS, Wahner HW, Melton LJ, III, Riggs BL (1984) Relative contributions of aging and estrogen deficiency to postmenopausal bone loss. N Engl J Med 311:1273–1275
Abyad A, Boyer JT (1992) Arthritis and aging. Curr Opin Rheumatol 4:153–159
Dequeker J, Mokassa L, Aerssens J (1995) Bone density and osteoarthritis. J Rheumatol 22:98–100
Fazzalari NL, Parkinson IH (1998) Femoral trabecular bone of osteoarthritic and normal subjects in an age and sex matched group. Osteoarthr Cartil 6:377–382
Fazzalari NL, Forwood MR, Smith K, Manthey BA, Herreen P (1998) Assessment of cancellous bone quality in severe osteoarthrosis: bone mineral density, mechanics, and microdamage. Bone 22:381–388
Li B, Aspden RM (1997) Composition and mechanical properties of cancellous bone from the femoral head of patients with osteoporosis or osteoarthritis. J Bone Miner Res 12:641–651
Page WF, Hoaglund FT, Steinbach LS, Heath AC (2003) Primary osteoarthritis of the hip in monozygotic and dizygotic male twins. Twin Res 6:147–151
Wheeless CR (2005) Wheeless’ Textbook of Orthopaedics. Available at: http://www.wheelessonline.com
Parfitt AM (1994) Osteonal and hemi-osteonal remodelling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem 55:273–286
Petrtyl M, Hert J, Fiala P (1996) Spatial organization of the Haversian bone in man. J Biomech 29:161–169
Smit TH, Burger EH (2000) Is BMU-coupling a strain-regulated phenomenon? A finite element analysis. J Bone Miner Res 15:301–307
Lanyon LE (1987) Functional strain in bone tissue as an objective, and controlling stimulus for adaptive bone remodeling. J Biomech 20:1083–1093
Huiskes R, Ruimerman R, Lenthe van GH, Janssen JD (2000) Effects of mechanical forces on maintenance and adaptation of form in trabecular bone. Nature 405:704–706
Cowin SC, Moss-Salentijn L, Moss ML (1991) Candidates for the mechanosensory system in bone. J Biomech Eng 113:191–197
Lanyon LE (1993) Osteocytes, strain detection, bone modeling and remodeling. Calcif Tissue Int 53:S102–S106
Burger EH, Klein-Nulend J (1999) Mechanotransduction in bone - role of the lacuno-canalicular network. FASEB J 13:S101–S112
Piekarski K, Munro M (1977) Transport mechanism operating between blood supply and osteocytes in long bones. Nature 269:80–82
Cowin SC, Weinbaum S (1998) Strain amplification in the bone mechanosensory system. Am J Med Sci 316:184–188
Knothe Tate ML, Knothe U (2000) An ex vivo model to study transport processes and fluid flow in loaded bone. J Biomech 33:247–254
Klein-Nulend J, Semeins CM, Ajubi NE, Nijweide PJ, Burger EH (1995) Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts: correlation with prostaglandin upregulation. Biochem Biophys Res Commun 217:640–648
Pitsillides AA, Rawlinson SC, Suswillo RF, Bourrin S, Zaman G, Lanyon LE (1995) Mechanical strain-induced NO production by bone cells: a possible role in adaptive bone (re)modeling? FASEB J 9:1614–1622
McAllister TN, Frangos JA (1999) Steady and transient fluid shear stress stimulate NO release in osteoblasts trough distinct biochemical pathways. J Bone Miner Res 14:930–936
Burger Eh, Klein-Nulend J, Smit TH (2003) Strain-derived canalicular fluid flow regulates osteoclastic activity in a remodeling osteon - a proposal. J Biomech 36:1453–1457
Forwood MR (1996) Inducible cyclo-oxygenase (COX-2) mediates the induction of bone formation by mechanical loading in vivo. J Bone Miner Res 11:1688–1693
Turner CH, Takano Y, Owan I, Murrell GA (1996) Nitric oxide inhibitor L-NAME suppresses mechanically induced bone formation in rats. Am J Physiol 270:E634–E639
Bakker AD, Klein-Nulend J, Burger EH (2003) Mechanotransduction in bone cells proceeds via activation of COX-2, but not COX-1. Biochem Biophys Res Commun 305:677–683
Sterck JG, Klein-Nulend J, Lips P, Burger EH (1998) Response of normal and osteoporotic human bone cells to mechanical stress in vitro. Am J Physiol 274:E1113–E1120
Lowry OH (1955) Micromethods for the assay of enzyme II specific procedure. Alkaline phosphatase. Meth Enzymol 4:371
Klein-Nulend J, van der Plas A, Semeins CM, Ajubi NE, Frangos JA, Nijweide PJ, Burger EH (1995) Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J 9:441–445
Klein-Nulend J, Helfrich MH, Sterck JG, MacPherson H, Joldersma M, Ralston SH, Semeins CM, Burger EH (1998) Nitric oxide response to shear stress by human bone cell cultures is endothelial nitric oxide synthase dependent. Biochem Biophys Res Commun 250:108–114
Bakker AD, Klein Nulend J, Tanck E, Albers GH, Lips P, Burger EH (2004) Additive effects of estrogen and mechanical loading on paracrine signaling by bone cells from osteoporotic donors. Osteoporosis Int 16(8):983–989. 10.1007/s00198-004-1785-0
Westbroek I, Ajubi NE, Alblas MJ, Semeins CM, Klein-Nulend J, Burger EH, Nijweide PJ (2000) Differential stimulation of prostaglandin G/H synthase-2 in osteocytes and other osteogenic cells by pulsating fluid flow. Biochem Biophys Res Commun 268:414–419
Homminga J, Weinans H, Gowin W, Felsenberg D, Huiskes R (2001) Osteoporosis changes the amount of vertebral trabecular bone at risk of fracture but not the vertebral load distribution. Spine 26:1555–1561
MacIntyre I, Zaidi M, Towhidul Alam ASM, Datta HK, Moonga BS, Lidbury P, Hecker M, Vane JR (1991) Osteoclastic inhibition:An action of nitric oxide not mediated by cyclic GMP. Proc Natl Acad Sci USA 88:2936–2940
Wimalawansa SL (2000) Nitroglycerin therapy is as efficacious as standard estrogen replacement therapy (premarin) in prevention of oophorectomy-induced bone loss: a human pilot clinical study. J Bone Miner Res 15:2240–2244
Ke HZ, Jee WS (1992) Effects of daily administration of prostaglandin E2 and its withdrawal on the lumbar vertebral bodies in male rats. Anat Rec 234:172–182
Li J, Burr DB, Turner CH (2002) Suppression of prostaglandin synthesis with NS-398 has different effects on endocortical and periosteal bone formation induced by mechanical loading. Calcif Tissue Int 70:320–329
Acknowledgements
The authors would like to thank H.F. Teshale, and C.M. Semeins for their technical assistance, and H.W. van Essen for his advice on performing the real-time PCRs. The Netherlands Organization for Scientific Research supported the work of A.D. Bakker and E. Tanck (NWO Grant 903-41-193). The European Community supported the work of J. Klein-Nulend (Fifth Framework grant QLK3-1999-00559).
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Bakker, A.D., Klein-Nulend, J., Tanck, E. et al. Different responsiveness to mechanical stress of bone cells from osteoporotic versus osteoarthritic donors. Osteoporos Int 17, 827–833 (2006). https://doi.org/10.1007/s00198-006-0072-7
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DOI: https://doi.org/10.1007/s00198-006-0072-7