This report indicates that mechanical loading of osteoblasts results in activation of PGD(2) and the concomitant expression of transcription factor PPARgamma-1 mRNA. The coordinated synthesis of Delta(12)PGJ(2), a natural ligand for PPARgamma-1, with the increased expression of PPARgamma-1, suggests that biomechanical transduction pathways that initially involve the activation of cyclooxygenases may also involve the activation of the Delta(12)PGJ(2)-PPAR pathway.
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 D2 synthase and increases the levels of prostaglandin D2 and its Δ12prostaglandin J2 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 Δ12prostaglandin J2‐dependent synthesis of bone morphogenetic proteins. Our goal was to investigate the molecular events involved in osteogenesis induced by mechanical loading and Δ12prostaglandin J2, namely the induction of bone morphogenetic proteins and peroxisome proliferator‐activated receptor γ‐1, a nuclear receptor for Δ12prostaglandin J2.
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 Δ12prostaglandin J2 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 Δ12prostaglandin J2. Δ12Prostaglandin J2 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 D2 synthase activation, induction of Δ12prostaglandin J2 and its nuclear receptor, peroxisome proliferator‐activated receptor γ‐1, and increased expression of bone morphogenetic protein‐2. These data suggest that the Δ12prostaglandin J2/peroxisome proliferator‐activated receptor γ‐1/bone morphogenetic protein‐2 pathway plays an important role in osteogenesis.
These results suggest that the osteoblastic biomechanical pathways that trigger bone formation involve cyclooxygenase and prostaglandin D2 synthase activation, induction of Delta12prostaglandin J2 and its nuclear receptor, peroxisome proliferator-activated receptor gamma-1, and increased expression of bone morphogenetic protein-2. These data suggest that the Delta12prostaglandin J2/peroxisome proliferator-activated receptor gamma-1/bone morphogenetic protein-2 pathway plays an important role in osteogenesis.
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