Effect of polymer molecular weight and addition of calcium stearate on response of MG63 osteoblast-like cells to UHMWPE particles
D. D. Dean
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Search for more papers by this authorC. H. Lohmann
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Orthopaedics, Georg-August Universität, Göttingen, Germany
Search for more papers by this authorV. L. Sylvia
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Search for more papers by this authorG. Köster
Department of Orthopaedics, Georg-August Universität, Göttingen, Germany
Search for more papers by this authorY. Liu
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Search for more papers by this authorZ. Schwartz
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Periodontics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Periodontology, Hebrew University Hadassah Faculty of Dental, Medicine, Jerusalem, Israel
Search for more papers by this authorCorresponding Author
B. D. Boyan
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Periodontics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Biochemistry, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA, Tel.: +1-210-567-6326; fax: +1-210-567-6295Search for more papers by this authorD. D. Dean
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Search for more papers by this authorC. H. Lohmann
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Orthopaedics, Georg-August Universität, Göttingen, Germany
Search for more papers by this authorV. L. Sylvia
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Search for more papers by this authorG. Köster
Department of Orthopaedics, Georg-August Universität, Göttingen, Germany
Search for more papers by this authorY. Liu
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Search for more papers by this authorZ. Schwartz
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Periodontics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Periodontology, Hebrew University Hadassah Faculty of Dental, Medicine, Jerusalem, Israel
Search for more papers by this authorCorresponding Author
B. D. Boyan
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Periodontics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Biochemistry, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Mail Code 7774, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA, Tel.: +1-210-567-6326; fax: +1-210-567-6295Search for more papers by this authorAbstract
Periprosthetic osteolysis and implant loosening is associated with the presence of ultrahigh molecular weight polyethylene (UHMWPE) wear debris particles. Osteoblast phenotypic expression in vitro is affected by UHMWPE particles, suggesting that bone formation may also be affected by wear debris. Here we tested the hypothesis that the response of osteoblasts to UHMWPE can be modified by changes in UHMWPE particle chemistry. We used four different commercially available preparations of GUR UHMWPE particles to determine if chemical composition (±Ca-stearate) or polymer molecular weight (3.1–4.2 million or 5.4–6.5 million g/mol) modulates osteoblast response. Particles were characterized by size distribution, morphology, and number of particles added to the culture medium. They had an average equivalent circle diameter ranging from 0.46–1.26 μm. MG63 cell response was assessed by measuring cell number, cellular and cell layer alkaline phosphatase, and prostaglandin E2 (PGE2) production. There were dose-dependent effects of the particles on cell response. Cell number and PGE2 production were increased, while alkaline phosphatase specific activity was decreased. In addition, there was a marked difference between cultures treated with particles containing Ca-stearate and as a function of polymer molecular weight. Particles of higher molecular weight caused a greater stimulation of proliferation and inhibition of alkaline phosphatase than particles of lower molecular weight. The presence of Castearate exerted a more pronounced depression of osteoblast phenotype as well as a significantly greater increase in PGE2 release by the cells. The present study shows that chemical composition and polymer molecular weight of UHMWPE are capable of modulating osteoblast response to particles. The results suggest that osteoblast differentiation is inhibited by UHMWPE particles, whereas cell proliferation and PGE2 production are stimulated. This may have direct effects on osteoblasts and bone formation, but also paracrine effects on cells of the monocytic lineage inducing bone resorption and promoting inflammation which may lead to aseptic loosening. The present results suggest that the cellular events in aseptic loosening may be modulated or even accelerated by changes in the composition of the UHMWPE used to fabricate implants. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
References
- 1 Allen MJ, Myer BJ, Millett PJ, Rushton N. The effects of particulate cobalt, chromium, and cobalt-chromium alloy on human osteoblast-like cells in vitro. J Bone Jt Surg (Br) 1997; 79: 475–82.
- 2 Boyan BD, Schwartz Z, Bonewald LF, Swain LD. Localization of 1,25-(OH)2D3 responsive alkaline phosphatase in osteoblast-like cells (ROS 17/2.8, MG 63, and MC 3T3) and growth cartilage cells in culture. J Biol Chem 1989; 264: 11879–86.
- 3 Boyan BD, Schwartz Z, Swain LD, Carnes Jr DL, Zislis T. Differential expression of phenotype by resting zone and growth region costochondral chondrocytes in vitro. Bone 1988; 9: 185–194.
- 4 Braun G, Kohavi D, Amir D, Luna MH, Caloss R, Sela J, Dean DD, Boyan BD, Schwartz Z. Markers of primary mineralization are correlated with bone-bonding ability of titanium or stainless steel in vivo. Clin Oral Implants Res 1995; 6: 1–13.
- 5 Bretaudiere JP, Spillman T. Alkaline phosphatases. In: HU Bergmeyer, editor. Methods of enzymatic analysis, vol 4 Weinheim, Germany: Verlag Chemica; 1984. p. 75–92.
- 6 Bruce JS, Salter AM. Metabolic fate of oleic acid, palmitic acid and stearic acid in cultured hamster hepatocytes. Biochem J 1996; 316: 847–52.
- 7 Campbell P, Ma S, Yeom B, McKellop H, Schmalzried TP, Amstutz HC. Isolation of predominantly submicron-sized UHMWPE wear particles from periprosthetic tissues. J Biomed Mat Res 1995; 29: 127–31.
- 8 Canuti RA, Paradisi L, Muzio G, Maggiora M, Mengozzi G, Garramone A, Dianzani MU. Changes of adenylate cyclase activity in AH-130 ascites hepatoma of Yoshida induced by enrichment with fatty acids. Biochem Biophys Res Commun 1995; 213: 853–60.
- 9 Cardoso CM, De Meis L. Modulation by fatty acids of Ca2+ fluxes in sarcoplasmic-reticulum vesicles. Biochem J 1993; 296: 49–52.
- 10 Dean DD, Schwartz Z, Blanchard CR, Liu Y, Agrawal CM, Lohmann CH, Sylvia VL, Boyan BD. Ultrahigh molecular weight polyethylene (UHMWPE) particles have direct effects on proliferation, differentiation, and local factor production of MG63 osteoblast-like cells. J Orthop Res 1999; 17: 9–17.
- 11 Dean DD, Schwartz Z, Bonewald LF, Muniz OE, Morales SM, Gomez R, Brooks BP, Qiao M, Howell DS, Boyan BD. Matrix vesicles produced by osteoblast-like cells in culture become significantly enriched in proteoglycan-degrading metalloproteinases after addition of b-glycerophosphate and ascorbic acid. Calcif Tissue Int 1994; 54: 399–408.
- 12 Dean DD, Schwartz Z, Liu Y, Blanchard CR, Agrawal CM, Mabrey JD, Sylvia VL, Lohmann CH, Boyan BD. The effect of ultrahigh molecular weight polyethylene wear debris on MG63 osteosarcoma cells in vitro. J Bone Jt Surg (Am) 1999; 81: 452–61.
- 13
Dziak RM.
Prostaglandins as mediators of bone cell metabolism.
In: RP Rubin,
GB Weiss,
JW Putney, editors.
Calcium in biological systems.
New York: Plenum Publishing:
1985.
p. 533–9.
10.1007/978-1-4613-2377-8_57 Google Scholar
- 14 Fermor BF, Masters JR, Wood CB, Miller J, Apostolov K, Habib NA. Fatty acid composition of normal and malignant cells and cytotoxicity of stearic, oleic and sterculic acids in vitro. Eur J Cancer 1992; 28A: 1143–7.
- 15 Franceschi RT, James WM, Zerlauth G. La.25-dihydroxyvitamin D3 specific regulation of growth, morphology, and fibronectin in a human osteosarcoma cell line. J Cell Physiol 1985; 123: 401–9.
- 16 Goldring SR, Schiller AL, Roelke M, Rourke CM, O'Neil DA, Harris WH. The synovial-like membrane at the bone-cement interface in loose total hip replacements and its proposed role in bone lysis. J Bone Jt Surg (Am) 1983; 65: 575–84.
- 17
Goodman S,
Aspenberg P,
Song Y,
Knoblich G,
Huie P,
Regula D,
Lidgren L.
Tissue ingrowth and differentiation in the boneharvest chamber in the presence of cobalt–chromium-alloy and high-density-polyethylene particles.
J Bone Jt Surg
1995;
77-A: 1025–35.
10.2106/00004623-199507000-00008 Google Scholar
- 18 Goodman S, Aspenberg P, Song Y, Regula D, Lidgren L. Polyethylene and titanium alloy particles reduce bone formation. Dose-dependence in bone harvest chamber experiments in rabbits. Acta Orthop Scand 1996; 67: 599–605.
- 19 Goodman SB, Lind M, Song Y, Smith RL. In vitro, in vivo, and tissue retrieval studies on particulate debris. Clin Orthop Rel Res 1998; 352: 25–34.
- 20 Hale LV, Kemick ML, Wuthier RE. Effect of vitamin D metabolites on the expression of alkaline phosphatase activity by epiphyseal hypertrophic chondrocytes in primary cell culture. J Bone Miner Res 1986; 1: 489–95.
- 21 Harmand MF. In vitro study of biodegradation of a Co–Cr alloy using a human cell culture model. J Biomater Sci Polymer Edition 1995; 6: 809–14.
- 22 Haynes DR, Hay SJ, Rogers SD, Ohta S, Howie DW, Graves SE. Regulation of bone cells by particle-activated mononuclear phagocytes. J Bone Jt Surg (Br) 1997; 79: 988–94.
- 23 Haynes DR, Rogers SD, Hay S, Pearcy MJ, Howie DW. The differences in toxicity and release of bone-resorbing mediators induced by titanium and cobalt–chromium-alloy wear particles. J Bone Jt Surg (Am) 1993; 75: 825–34.
- 24 Horowitz SM, Gonzales JB. Inflammatory response to implant particulates in a macrophage/osteoblast coculture model. Calcif Tissue Int 1996; 59: 392–6.
- 25 Hsiao WL, Pai HL, Matsui MS, Weinstein IB. Effects of specific fatty acids on cell transformation induced by activated c-H-ras oncogene. Oncogene 1990; 5: 417–21.
- 26 Hukkanen M, Corbett SA, Batten J, Konttinen YT, McCarthy ID, Maclouf J, Santavirta S, Hughes SP, Polak JM. Aseptic loosening of total hip replacemen. Macrophage expression of inducible nitric oxide synthase and cyclo-oxygenase-2, together with peroxynitrite formation, as a possible mechanism for early prosthesis failuret. J Bone Joint Surg (Br) 1997; 79: 467–74.
- 27
Kieswetter K,
Schwartz Z,
Hummert TW,
Cochran DL,
Simpson J,
Dean DD,
Boyan BD.
Surface roughness modulates the local production of growth factors and cytokines by osteoblast-like MG63 cells.
J Biomed Mater Res
1996;
32: 55–63.
10.1002/(SICI)1097-4636(199609)32:1<55::AID-JBM7>3.0.CO;2-O CAS PubMed Web of Science® Google Scholar
- 28
Klein-Nulend J,
Semeins CM,
Burger EH.
Prostaglandin-mediated modulation of transforming growth factor-beta.
J Cell Physiol
1996;
168: 1–7.
10.1002/(SICI)1097-4652(199607)168:1<1::AID-JCP1>3.0.CO;2-T CAS PubMed Web of Science® Google Scholar
- 29 Klein DC, Raisz LG. Prostaglandins: Stimulation of bone resorption in tissue culture. Endocrinology 1970; 86: 1436–40.
- 30 Kwon SY, Wood DJ, Takei H, Pioletti D, Akeson W, Sung K-LP. Titanium debris inhibits osteoblast adhesion to fibronectin substrates in vitro. Trans Orthop Res Soc 1999; 24: 30.
- 31 Lincks J, Boyan BD, Blanchard CR, Lohmann CH, Liu Y, Cochran DL, Dean DD, Schwartz Z. Response of MG63 osteoblast-like cells to titanium and titanium alloy is dependent on surface roughness and composition. Biomaterials 1998; 19: 2219–32.
- 32 Lohmann CH, Schwartz Z, Köster G, Jahn U, Buchhorn GH, MacDougall MJ, Casasola D, Liu Y, Sylvia VL, Dean DD, Boyan BD. Phagocytosis of wear debris by osteoblasts affects differentiation and local factor production in a manner dependent on particle composition. Biomaterials 2000; 21: 551–61.
- 33 Maloney WJ, Smith RL, Schmalzried TP, Chiba J, Huene D, Rubash H. Isolation and characterization of wear particles generated in patients who have had failure of a hip arthroplasty without cement. J Bone Jt Surg (Am) 1995; 77: 1301–10.
- 34 Marshall TS, Schwartz Z, Swain LD, Amir D, Sela J, Gross U, Mueller-Mai C, Boyan BD. Matrix vesicle enzyme activity in endosteal bone following implantation of bonding and nonbonding implant materials. Clin Oral Implants Res 1991; 2: 112–20.
- 35 Martin JY, Schwartz Z, Hummert TW, Schraub DM, Simpson J, Lankford J, Dean DD, Cochran DL, Boyan BD. Effect of titanium surface roughness on proliferation, differentiation, and protein synthesis of human osteoblast-like cells (MG63). J Biomed Mater Res 1995; 29: 389–401.
- 36 McKellop HA, Campbell P, Park SH, Schmalzried TP, Grigoris P, Amstutz HC, Sarmiento A. The origin of submicron polyethylene wear debris in total hip arthroplasty. Clin Orthop Rel Res 1995; 311: 3–20.
- 37 McKellop HA, Shen FW, Campbell P, Ota T. Effect of molecular weight, calcium stearate, and sterilization methods on the wear of ultra high molecular weight polyethylene acetabular cups in a hip joint. J Orthop Res 1999; 17: 329–39.
- 38 Muratoglu OK, Jasty M, Harris WH. High resolution synchrotron infrared microscopy of the structure of fusion defects in UHMWPE. Trans Orthop Res Soc 1997; 22: 773.
- 39 Nefussi JR, Baron R. PGE2 stimulates both resorption and formation of bone in vitro: differential responses of the periosteum and the endosteum in fetal rat long bone cultures. Anat Rec 1985; 211: 9–16.
- 40 Poggie RA, Takeuchi MT, Averill R. Effects of resin type, consolidation method, and sterilization of UHMWPE. Trans Soc Biomater 1997; 20: 216.
- 41 Raisz LG, Fall PM. Biphasic effects of prostaglandin E2 on bone formation in cultured fetal rat calvariae: interaction with cortisol. Endocrinology 1990; 126: 1654–9.
- 42 Reilly SS, Ramp WK, Zane SF, Hudson MC. Internalization of Staphylococcus aureus by embryonic chicken osteoblasts in vivo. J Bone Miner Res 1997; 12: S410.
- 43
Sacomen D,
Smith RL,
Song Y,
Fornasier V,
Goodman SB.
Effects of polyethylene particles on tissue surrounding knee arthroplasties in rabbits.
J Biomed Mater Res
1998;
43: 123–30.
10.1002/(SICI)1097-4636(199822)43:2<123::AID-JBM6>3.0.CO;2-Q CAS PubMed Web of Science® Google Scholar
- 44 Schmidt MB, Hamilton JV. The effects of calcium stearate on the properties of UHMWPE. Trans Orthop Res Soc 1996; 21: 22.
- 45 Schwartz Z, Dennis R, Bonewald LF, Swain LD, Gomez R, Boyan BD. Differential regulation of prostaglandin E2 synthesis and phospholipase A2 activity by 1,25-(OH)2 D3 in three osteoblast-like cell lines (MC-3T3-E1, ROS 17/2.8, and MG-63). Bone 1992; 13: 51–8.
- 46 Schwartz Z, Knight G, Swain LD, Boyan BD. Localization of vitamin D3-responsive alkaline phosphatase in cultured chondrocytes. J Biol Chem 1988; 263: 6023–6.
- 47 Schwartz Z, Swain LD, Marshall TS, Sela J, Gross U, Amir D, Mueller-Mai C, Boyan BD. Modulation of matrix vesicle enzyme activity and phosphatidylserine content by ceramic implant materials during endosteal bone healing. Calcif Tissue Int 1992; 51: 429–37.
- 48 Shanbhag AS, Jacobs JJ, Glant TT, Gilbert JL, Black J, Galante JO. Composition and morphology of wear debris in failed uncemented total hip replacement. J Bone Joint Surg 1994; 76B: 60–7.
- 49
Takahashi T,
So S,
Ikeuchi T,
Takahashi K,
Kumegawa M.
Collagen phagocytosis by osteoblast-like cells of mouse calvaria in vitro: an electron microscopic study.
J Jpn Assoc Periodontol
1984;
26: 710–25.
10.2329/perio.26.710 Google Scholar
- 50 Tanner MG, Whiteside LA, White SE. Effect of polyethylene quality on wear in total knee arthroplasty. Clin Orthop 1995; 317: 83–8.
- 51 Willert HG, Bertram H, Buchhorn GH. Osteolysis in alloarthroplasty of the hip. The role of ultra-high-molecular weight polyethylene wear particles. Clin Orthop Rel Res 1990; 258: 95–107.
- 52 Willie BM, Whitfield JR, Bloebaum RD, Hofmann AA. Quantitative analysis of calcium stearate particles in retrieved patellar components. Trans Orthop Res Soc 1999; 24: 836.
- 53 Wirth MA, Agrawal CM, Mabrey JD, Dean DD, Blanchard CR, Miller MA, Rockwood Jr CA. Isolation and characterization of polyethylene wear debris associated with osteolysis following total shoulder arthroplasty. J Bone Jt Surg (Am) 1999; 81: 29–37.
- 54 Yao J, Cs-Szabo G, Jacobs JJ, Kuettner KE, Glant TT. Suppression of osteoblast function by titanium particles. J Bone Jt Surg (Am) 1997; 79: 107–12.
- 55 Yao J, Glant TT, Lark MW, Mikecz K, Jacobs JJ, Hutchinson NI, Hoerrner LA, Kuettner KE, Galante JO. The potential role of fibroblasts in periprosthetic osteolysis: fibroblast response to titanium particles. J Bone Miner Res 1995; 10: 1417–27.