Prostaglandin F2α: A bone remodeling mediator

Abstract

Prostaglandin F2α (PGF2α) plays multiple roles on bone metabolism by regulating a wide range of signaling pathways. PGF2α, via activation of PKC, stimulates Na-dependent inorganic phosphate (Pi) transport system in osteoblasts; up-regulates interleukin (IL)-6 synthesis; increases vascular endothelial growth factor (VEGF). In addition, PGF2α acts as a strong mitogenic and survival agent on osteoblasts, and these effects are, at least in part, mediated by the binding of fibroblast growth factor-2 (FGF-2) to the specific receptor FGFR1. The understanding of PGF2α intracellular network, albeit complex to clarify, provides molecular bases useful to identify the players of osteoblast proliferation, apoptosis, and the associated angiogenic processes. Indeed, the molecular mechanism that underline PGF2α-regulated bone metabolism may be a promising platform for the development of novel targeted therapies in the treatment of bone disorders and disease.

The dual face of parathyroid hormone and prostaglandins in the osteoimmune system

“…The current findings concur that osteoblasts are recruited in distinct areas called "basic multicellular units" by osteoclasts via cross-talk between both cell types and begin to lay down new bone matrixes (14,25). This complex and dynamic equilibrium of bone cells is regulated by several systemic factors, such as bone morphogenetic proteins (68,97,102,146), parathyroid hormone (PTH) (39,73,100), and prostaglandins (PGs) (3,4,99,101), as well as shared cytokines, transcription factors, and membrane receptors in the immune and skeletal systems (49,123). Modern research has argued that these two systems interact with each other and that impaired cross-talk between the distinct niches in the marrow creates pathological conditions like chronic inflammatory joint diseases, known as rheumatoid arthritis (RA) (27,38) and chronic arthritis (16), which lead to decreased bone density and alter the mechanical properties of the bone itself.…”

“…Thus far, PGE 2 is able to modulate various processes in a scenario-dependent manner, and its regulatory role in hematopoiesis has been well documented for more than three decades (83,84). Concerning the osteoblast/osteoclast metabolism, we and others showed that PGs such as PGE 2 and PGF2␣ exert both stimulatory and inhibitory effects on bone formation in cell and organ culture (3,4,91,92,99,101), acting in an autocrine and/or paracrine manner (86). Suda et al (115) have also reported that IL-6 can stimulate osteoblasts to induce RANKL expression through a PGE 2 -related mechanism and, consequently, osteoclastogenesis.…”

“…Our previous findings revealed that PGF2␣ acts as a strong mitogenic and survival agent on osteoblasts, and these effects are (at least in part) mediated by FGF-2 (3,4,98,99,101). FGF-2 is a well-studied anabolic bone agent that promotes bone formation by stimulating the proliferation and differentiation of MSCs (69,134).…”

Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts

“…Prostaglandins, which have previously been recognized as potent bone-resorptive agents (8), are known to play important roles also in the process of bone formation (8,9). Of the prostaglandins, prostaglandin F 2α (PGF 2α ) has been shown to act as a bone remodeling mediator (9).…”

“…Prostaglandins, which have previously been recognized as potent bone-resorptive agents (8), are known to play important roles also in the process of bone formation (8,9). Of the prostaglandins, prostaglandin F 2α (PGF 2α ) has been shown to act as a bone remodeling mediator (9). In relation to osteoblasts, we have previously demonstrated that PGF 2α induces activation of p38 mitogen-activated protein (MAP) kinase, p44/p42 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblastlike MC3T3-E1 cells, and that PGF 2α -induced osteoprotegerin synthesis is mediated through these MAP kinases (10).…”