Endothelin-1 actions on resorption, collagen and noncollagen protein synthesis, and phosphatidylinositol turnover in bone organ cultures.

Abstract

The effects of endothelin-1 (ET) on several tissues are mediated by prostaglandins. In this study, we investigated the actions of ET on bone and determined whether they are mediated through prostaglandin-dependent pathways. Bone resorption, collagen, and non-collagen protein synthesis and inositol phosphate (IP) production were studied in neonatal mouse calvaria and fetal rat limb bone cultures. The effects of ET in the calvaria model were examined in the presence or absence of the cyclooxygenase inhibitor indomethacin (INDO). Bone resorption was stimulated by ET in the neonatal mouse calvaria, and this effect was inhibited by INDO. 45Ca release in the fetal rat limb bones was not affected by ET. ET stimulated collagen and noncollagen protein synthesis significantly in the calvaria model in the presence but not in the absence of INDO, suggesting that the anabolic effects of ET were masked by endogenous prostaglandin production. ET increased phosphatidylinositol turnover in both bone organ cultures. Although the addition of INDO reduced IP production slightly in the mouse calvaria, it was still significantly stimulated by ET. Our results demonstrate that ET has marked effects on bone tissue in vitro. Effects on resorption appear to be prostaglandin dependent, whereas the anabolic effects were not prostaglandin mediated. The stimulatory effects of ET on protein synthesis could be mediated through the IP signaling pathway. Since ET stimulates both bone resorption and anabolism, this peptide may have a role in the coupling of bone remodeling.

Osteoclast Responses to Lipopolysaccharide, Parathyroid Hormone and Bisphosphonates in Neonatal Murine Calvaria Analyzed by Laser Scanning Confocal Microscopy

“…Notably, bone formation activity was increased in association with bone resorptive activity induced by LPS and PTH (Suzuki et al 2003), consistent with the concept that the activities of osteoblasts and osteoclasts are coupled. Although it was not possible to quantify bone resorption by measuring differences in the thickness of the calvaria before and after inducing bone resorption by morphometry, the inclusion of biochemical analyses (Tatrai et al 1992) in future studies should circumvent these problems.…”

Comparison of plasma endothelin levels between osteoporotic, osteopenic and normal subjects

“…ET stimulates proliferation of the capillary endothelial cells [2,13-15], osteoblasts and osteoprogenitor cells [3,16]. They also stimulate differentiation of osteoprogenitor cells to osteoblasts [3,4,6]. …”

“…Osteoblastic activity is increased by ET as this effect is demonstrated by stimulation of synthesis of collagen and non-collagen proteins [6] as well as osteocalcin and osteopontin messages in bone tissue [17]. …”

Osteopenia and endothelin-1-mediated vasconstrictor tone in postmenopausal women

“…Both bone and parathyroid cells contain ET receptors and synthesize and release ET-1 [22–26]. ET-1 can stimulate osteoblast proliferation and differentiation in vitro [27].…”