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Mechanical loading and Δ 12 prostaglandin J 2 induce bone morphogenetic protein‐2, peroxisome proliferator‐activated receptor γ‐1, and bone nodule formation in an osteoblastic cell line
Author(s) -
Siddhivarn C.,
Banes A.,
Champagne C.,
Riché E. L.,
Weerapradist W.,
Offenbacher S.
Publication year - 2007
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2006.00965.x
Subject(s) - bone morphogenetic protein , peroxisome proliferator activated receptor , bone morphogenetic protein 2 , medicine , endocrinology , receptor , prostaglandin e2 , chemistry , prostaglandin , biology , microbiology and biotechnology , biochemistry , in vitro , gene
Background and Objective: We have previously reported that mechanical strain applied at a 1% level to an osteoblastic cell line induces the transcription of prostaglandin D 2 synthase and increases the levels of prostaglandin D 2 and its Δ 12 prostaglandin J 2 metabolite. Mechanical strain also induces the expression of peroxisome proliferator‐activated receptor γ‐1 and bone nodule formation. We hypothesized that mechanical load induces bone formation via Δ 12 prostaglandin J 2 ‐dependent synthesis of bone morphogenetic proteins. Our goal was to investigate the molecular events involved in osteogenesis induced by mechanical loading and Δ 12 prostaglandin J 2 , namely the induction of bone morphogenetic proteins and peroxisome proliferator‐activated receptor γ‐1, a nuclear receptor for Δ 12 prostaglandin J 2 . Material and Methods: Osteoblast monolayers were stretched for 1 h with a 1‐h resting period and stretched for another hour at 1 Hz with 1% elongation. Cells were collected 0, 1, 6 and 16 h after stretching. Cyclooxygenase inhibitors and Δ 12 prostaglandin J 2 were added in some experiments. Relative quantitative reverse transcriptase‐polymerase chain reaction was used to examine whether the mRNA of bone morphogenetic protein‐2, ‐4, ‐6, ‐7 and peroxisome proliferator‐activated receptor γ‐1 was induced. Immunohistochemistry was used to evaluate bone morphogenetic protein expression in cells. Results: Mechanical strain significantly increased the mRNA expression of bone morphogenetic protein‐2, ‐6, ‐7 and of peroxisome proliferator‐activated receptor γ‐1, but not of bone morphogenetic protein‐4. In stretched cells, bone morphogenetic protein‐2 and peroxisome proliferator‐activated receptor γ‐1 expression was blocked by cyclooxygenase inhibitors, but restored by exogenous Δ 12 prostaglandin J 2 . Δ 12 Prostaglandin J 2 significantly enhanced bone nodule formation and bone morphogenetic protein‐2 expression when added alone to resting osteoblasts. Conclusion: These results suggest that the osteoblastic biomechanical pathways that trigger bone formation involve cyclooxygenase and prostaglandin D 2 synthase activation, induction of Δ 12 prostaglandin J 2 and its nuclear receptor, peroxisome proliferator‐activated receptor γ‐1, and increased expression of bone morphogenetic protein‐2. These data suggest that the Δ 12 prostaglandin J 2 /peroxisome proliferator‐activated receptor γ‐1/bone morphogenetic protein‐2 pathway plays an important role in osteogenesis.