PGE2 prevents calcification while PGD2 causes calcification

Abstract
Objective—
Chronic administration of selective cyclooxygenase-2 (COX-2) inhibitors leads to an increased risk of adverse cardiovascular events, including myocardial infarction and stroke. Vascular smooth muscle cell (VSMC) calcification, a common complication of chronic kidney disease, is directly related to cardiovascular morbidity and mortality. Here, we tested whether specific COX-2 inhibition affects vascular calcification during chronic renal failure.

Approach and Results—
The COX-2–specific inhibitors NS398 and SC236 significantly increased high–phosphate (Pi)-induced VSMC calcification. Similarly, COX-2−/− VSMCs, COX-2−/− aortas rings treated with high Pi and adenine diet–induced COX-2−/− chronic renal failure mice displayed enhanced calcium deposition. Metabolomic analysis revealed the differential suppression of PGE2 production by COX-1– and COX-2–specific inhibitors in high–Pi-stimulated VSMCs, indicating the involvement of PGE2 during COX-2 inhibition-aggravated vascular calcification. Indeed, exogenous PGE2 reduced alkaline phosphatase activity, osteogenic transdifferentiation, apoptosis, and calcification of VSMCs. In accordance, downregulation of microsomal prostaglandin E synthase (mPGES)-1 in VSMCs, mPGES-1−/− aorta with high-Pi stimulation and mPGES-1−/− chronic renal failure mice resulted in enhanced vascular mineralization. Further applications of RNAi and specific antagonists for PGE2 receptors indicated EP4 may mediate PGE2-inhibited vascular calcification.

Conclusions—
Our data revealed the pivotal role of COX-2–mPGES-1–PGE2 axis in vascular calcification. The selective inhibition of COX-2 or mPGES-1 may increase the risk of calcification and subsequent adverse cardiovascular events during chronic renal failure


Maybe the reason PGE2 is beneficial for hair growth is that it mediate calcification in the scalp!


https://www.ncbi.nlm.nih.gov/pubmed/2930558
Prostaglandin D2 stimulates calcification of human osteoblastic cells.
Koshihara Y1, Kawamura M.
Author information
Abstract
Studies on prostaglandin (PG) regulation of bone formation and resorption metabolism have been complicated by the heterogeneity of the tissue, which involves the interaction between and the activities of two bone cell types, osteoblasts and osteoclasts. In a simplified assay system using a cultured human osteoblastic cell line which has the capacity to form calcified tissue, we determined the effects of PGs on calcification. Of the PGs tested, PGD2 has a remarkable stimulatory activity on osteoblast calcification, but that the effective form is probably a metabolite, delta 12-PGJ2. This calcification function is not cAMP-mediated. PGD2 acts directly on osteoblast to cause stimulation of calcification.