Prostaglandin F2α receptor (FP) signaling regulates Bmp signaling and promotes chondrocyte differentiation

• Published in: Biochimica et biophysica acta Vol. 1853; no. 2; pp. 500 - 512
• Main Authors: Kim, Joohwee, Shim, Minsub
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-02-2015
• Subjects: Animals; Bmp; Bone Morphogenetic Proteins - metabolism; Cartilage - metabolism; Cartilage - pathology; Cell Differentiation - genetics; Cell Line; Chondrocytes; Chondrocytes - cytology; Chondrocytes - metabolism; Chondrogenesis - genetics; Gene Knockdown Techniques; Metatarsal Bones - pathology; Mice, Inbred C57BL; Phosphorylation; Prostaglandin F2α; Receptors, Prostaglandin - genetics; Receptors, Prostaglandin - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - genetics; Smad Proteins - metabolism; Up-Regulation; FP; Bmp; Chondrocytes; Prostaglandin F2α; Prostaglandin F(2α)
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2014.12.003

Prostaglandins are a group of lipid signaling molecules involved in various physiological processes. In addition, prostaglandins have been implicated in the development and progression of diseases including cancer, cardiovascular disease, and arthritis. Prostaglandins exert their effects through the activation of specific G protein-coupled receptors (GPCRs). In this report, we examined the role of prostaglandin F2α receptor (FP) signaling as a regulator of chondrocyte differentiation. We found that FP expression was dramatically induced during the differentiation of chondrocytes and was up-regulated in cartilages. Forced expression of FP in ATDC5 chondrogenic cell line resulted in the increased expression of differentiation-related genes and increased synthesis of the extracellular matrix (ECM) regardless of the presence of insulin. Similarly, PGF2α treatment induced the expression of chondrogenic marker genes. In contrast, knockdown of endogenous FP expression suppressed the expression of chondrocyte marker genes and ECM synthesis. Organ culture of cartilage rudiments revealed that PGF2α induces chondrocyte hypertrophy. Additionally, FP overexpression increased the levels of Bmp-6, phospho-Smad1/5, and Bmpr1a, while knockdown of FP reduced expression of those genes. These results demonstrate that up-regulation of FP expression plays an important role in chondrocyte differentiation and modulates Bmp signaling.
•PGF2α receptor (FP) is highly induced during chondrogenic differentiation.•Forced expression of FP promotes chondrogenic differentiation.•PGF2α treatment enhances in vitro and ex vivo chondrogenic differentiation.•Knockdown of endogenous FP expression suppresses chondrogenic differentiation.•FP signaling regulates the expression of Bmp signaling components.