Scientific Article   |    
Nitric Oxide and Prostaglandin E2 Production in Response to Ultra-High Molecular Weight Polyethylene Particles Depends on Osteoblast Maturation State
Christoph H. Lohmann, MD; David D. Dean, PhD; Lynda F. Bonewald, PhD; Zvi Schwartz, DMDPhD; Barbara D. Boyan, PhD
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Investigation performed at the University of Texas Health Science Center at San Antonio, San Antonio, Texas

Christoph H. Lohmann, MD
Department of Orthopaedics, Universität Hamburg-Eppendorf, Martini Str. 52, D-20246 Hamburg, Germany

David D. Dean, PhD
Barbara D. Boyan, PhD
Departments of Orthopaedics (D.D.D. and B.D.B), Periodontics (B.D.B), and Biochemistry (B.D.B.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. E-mail address for D.D. Dean: deand@uthscsa.edu. E-mail address for B.D. Boyan: boyanb@uthscsa.edu

Lynda F. Bonewald, PhD
Department of Oral Biology, University of Missouri School of Dentistry, 650 East 25th Street, Kansas City, MO 64108-2784

Zvi Schwartz, DMD, PhD
Department of Periodontics, Hebrew University Hadassah Faculty of Dental Medicine, P.O. Box 12272, Jerusalem, Israel 91120

In support of their research or preparation of this manuscript, one or more of the authors received grants or outside funding from Aesculap AG (Tüttlingen, Germany), the Center for the Enhancement of the Biology-Biomaterials Interface at the University of Texas Health Science Center at San Antonio, and PHS grants DE-08603, DE-05937, and AR-42372. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

J Bone Joint Surg Am, 2002 Mar 01;84(3):411-419
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Background: Recent studies have shown that osteoblast-like cells respond directly to ultra-high molecular weight polyethylene particles in culture, suggesting that they may be involved in aseptic loosening of endoprostheses. We tested the hypothesis that the state of cell maturation plays a role in the response of osteogenic cells to ultra-high molecular weight polyethylene particles.

Methods: MG63 cells (immature osteoblast-like cells), OCT-1 cells (mature secretory osteoblast-like cells), and MLO-Y4 cells (osteocyte-like cells) were treated for twenty-four hours with commercial ultra-high molecular weight polyethylene particles with an average diameter of 1 mm. The effect of particle treatment on cell proliferation was assessed by measuring the number of cells, whereas the effects on differentiation and local factor production were assessed by measuring the production of osteocalcin, prostaglandin E2, and nitric oxide. The effect of particles on apoptosis was also evaluated.

Results: The addition of ultra-high molecular weight polyethylene particles increased the number of MG63 cells, did not affect the number of OCT-1 cells, and led to a decrease in the number of MLO-Y4 cells. The observed changes in cell number were not due to programmed cell death, as no more than 3% of the cells in cultures treated with the highest concentration of particles were undergoing apoptosis. Osteocalcin production was not affected by the addition of particles. Prostaglandin E2 production was increased in all three types of cultures, but the effect was greatest in OCT-1 cell cultures, as was the absolute amount of prostaglandin E2 produced. Nitric oxide production was unaffected in MG63 cell cultures, but it was stimulated in OCT-1 and MLO-Y4 cell cultures.

Conclusions: The results of the present study support the hypothesis that osteoblast cell maturation state plays an important role in the response to ultra-high molecular weight polyethylene particles and that the terminally differentiated osteocyte may be involved in the bone response to wear debris in vivo.

Clinical Relevance: Because maturation state in the osteoblast lineage is an important factor in the cellular response to wear debris and the osteocyte is surprisingly sensitive to ultra-high molecular weight polyethylene particles, and because these cells have been shown to be in direct contact with the bone-implant interface via canaliculi, their role in aseptic loosening needs to be considered.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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