Volume 17, Number 2, June 2005

Combination of Platelet-rich Plasma and Cyclooxygenase-2 Inhibitor Potently Stimulates Bone Marrow Stromal Cell Proliferation in Vitro

Daichi Chikazu, Shinsuke Ohba, Toru Ogasawara, Hideto Saijo, Yoshiyuki Mori, Ken Tomizuka, Hiroshi Kawaguchi, Yoshiyuki Yonehara, Takafumi Susami, Tsuyoshi Takato

Department of Oral-maxillofacial Surgery, Dentistry and Orthodontics, The University of Tokyo Hospital, Tokyo, Japan

Abstract
Objective:
To assess the effects of platelet-rich plasma on the proliferation of cultured mouse bone marrow stromal cells and on the production of cyclooxygenase-2 and prostaglandin E2 by these cells, and to determine whether the mitogenic activity of platelet-rich plasma is enhanced by combination with a selective cyclooxygenase-2 inhibitor.
Materials and Methods: A dish with 2 chambers, separated by a porous membrane, and platelet-rich plasma gel were used to assess the effects of platelet-rich plasma on cultured mouse bone marrow stromal cells in the absence of serum. The cells were cultured for 7 days with low (0.05 mL), medium (0.25 mL), or high (0.5 mL) volumes of platelet-rich plasma gel, and the effects on bone marrow stromal cell proliferation were examined. Concentrations of cyclooxygenase-2 and prostaglandin E2 in the culture media were assayed. The effect of celecoxib, a cyclooxygenase-2 inhibitor, on the mitogenic activity of platelet-rich plasma was examined. The mitogenic activity of platelet-rich plasma was compared between bone marrow stromal cells from cyclooxygenase-2–deficient mice and bone marrow stromal cells from wild-type littermates.
Results: Platelet-rich plasma stimulated bone marrow stromal cell proliferation over a 7-day period. Platelet-rich plasma potently increased the cyclooxygenase-2 mRNA level and prostaglandin E2 production, and endogenous prostaglandin E2 treatment inhibited the proliferation of bone marrow stromal cells. The cyclooxygenase-2 inhibitor celecoxib stimulated the mitogenic activity of platelet-rich plasma. The mitogenic activity of platelet-rich plasma that was added to the culture medium of bone marrow stromal cells derived from cyclooxygenase-2–deficient mice was approximately twice that of platelet-rich plasma added to the culture medium of bone marrow stromal cells derived from wild-type mice.
Conclusions: Platelet-rich plasma may directly induce bone formation by stimulating the proliferation of bone marrow stromal cells. Because cyclooxygenase-2 induction by platelet-rich plasma blunts its mitogenic activity, combination with a cyclooxygenase-2 inhibitor may enhance the osteogenic activity of platelet-rich plasma.

Key words: Blood platelets, Bone marrow cells, Cyclooxygenase 2, Plasma, Prostaglandins

Asian J Oral Maxillofac Surg. 2005;17:81-87.

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