Journal of Oral and Maxillofacial Surgery
Volume 67, Issue 11 , Pages 2412-2417, November 2009

Effect of Ibuprofen on Osteoblast Differentiation of Porcine Bone Marrow–Derived Progenitor Cells

  • Harutsugi Abukawa, DDS, PhD

      Affiliations

    • Instructor, Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo, Japan
    • ,
  • Maynard Phelps

      Affiliations

    • Student, Harvard School of Dental Medicine, Boston, MA
    • ,
  • Pamela Jackson

      Affiliations

    • Research Volunteer, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, MA
    • ,
  • R. Malcolm Smith, MD, FRCS

      Affiliations

    • Chief, Orthopedic Trauma Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA
    • ,
  • Joseph P. Vacanti, MD

      Affiliations

    • John Homans Professor of Surgery, Department of Surgery, and Director, Tissue Engineering and Organ Fabrication Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, MA
    • ,
  • Leonard B. Kaban, DMD, MD

      Affiliations

    • Walter C. Guralnick Professor and Chairman, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital and Harvard School of Dental Medicine, Boston, MA
    • ,
  • Maria J. Troulis, DDS, MSc

      Affiliations

    • Associate Professor and Director, Minimally Invasive Oral and Maxillofacial Surgery Program and Residency Program, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital and Harvard School of Dental Medicine, Boston, MA
    • Corresponding Author InformationAddress correspondence and reprint requests to Dr Troulis: Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Warren Bldg 1201, 55 Fruit St, Boston, MA 02114

Purpose

Nonsteroidal anti-inflammatory drugs are commonly prescribed to reduce inflammation and pain. However, little is known about the direct effect of these drugs on the differentiation of bone marrow–derived progenitor cells into osteoblasts. The purpose of this study was to determine the effect of ibuprofen on osteoblast differentiation and proliferation in a minipig model.

Materials and Methods

Bone marrow was aspirated from the minipig ilium, and porcine bone marrow–derived progenitor cells (pBMPCs) were isolated and expanded in standard culture medium. The pBMPCs were replated and differentiated into osteoblasts by use of osteogenic supplements (OS). Five groups were studied: negative control—pBMPCs in standard medium only; positive control—pBMPCs, standard culture medium, and OS; and 3 experimental groups—pBMPCs, standard culture medium, OS, and ibuprofen added in doses of 0.1, 1.0, and 3.0 mmol/L. Cell cultures were evaluated quantitatively by alkaline phosphatase (ALP) stain, von Kossa stain, and deoxyribonucleic acid (DNA) content.

Results

pBMPCs cultured with OS and low-dose ibuprofen (0.1 mmol/L) showed ALP stain, von Kossa stain, and DNA content similar to pBMPCs cultured in OS (positive control). pBMPCs cultured in higher doses of ibuprofen (1.0 and 3.0 mmol/L) produced significantly less positive staining of ALP and von Kossa and decreased DNA content.

Conclusion

The results indicate that high-dose ibuprofen has a deleterious effect on pBMPC differentiation into osteoblasts whereas low-dose ibuprofen does not. The low dose of 0.1 mmol/L is the typical serum level when prescribed for clinical use.

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 The project was supported in part by the Oral and Maxillofacial Surgery Foundation Student Research Training Award, the Department of Oral and Maxillofacial Surgery Education and Research Fund, the Massachusetts General Hospital Laboratory for Tissue Engineering and Organ Fabrication, and grants from the Hanson Foundation (Boston, MA) (M.J.T.) and Therics (Princeton, NJ).

PII: S0278-2391(09)01178-1

doi:10.1016/j.joms.2009.05.434

Journal of Oral and Maxillofacial Surgery
Volume 67, Issue 11 , Pages 2412-2417, November 2009

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