Effect of ibuprofen on osteoblast differentiation of porcine bone marrow-derived progenitor cells.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Abukawa
Harutsugi
H
Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo, Japan.
Phelps
Maynard
M
Jackson
Pamela
P
Smith
R Malcolm
RM
Vacanti
Joseph P
JP
Kaban
Leonard B
LB
Troulis
Maria J
MJ
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D013552:Swine; D013556:Swine, Miniature
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000469:Alkaline Phosphatase; D007052:Ibuprofen