Epidrugs: novel epigenetic regulators that open a new window for targeting osteoblast differentiation

摘要

Osteogenesis regulating signaling pathways. a Hedgehog signaling pathway: Hh, an important secreted molecule of the hedgehog family, regulates cell functions during bone formation. Hh, hedgehog; Shh, Sonic hedgehog; Ihh, Indian hedgehog, Dhh; Desert hedgehog; Ptc, patched; Smo, smoothened. b Notch signaling pathway: Notch signaling has a key role in cellular development and tissue morphogenesis. Runx2, runt-related transcription factor 2; ADAM, a disintegrin and metalloprotease; TACE, tumor necrosis factor-α converting enzyme; NICD, Notch intracellular domain; CSL, C protein binding factor 1/suppressor of Hairless/Lag-1; MAML, mastermind-like, HES, hairy and enhancer of split; HEY, HES-related with YRPW motif. c Wnt signaling pathway: Wnt signaling is another signaling pathway in development and skeletal pattern. The noncanonical signaling pathway plays a role in regulating the osteoblast lineage. FZD, frizzled; LRP5 or LRP6, lipoprotein receptor-related protein 5 or 6; GSK3, glycogen synthase kinase 3; JNK, c-Jun N-terminal kinase. d PTH/ PTHrP signaling pathway: PTH may have either catabolic or anabolic effects on bone formation, depending on its route of administration. PTH, parathyroid hormone; PTHrP, PTH-related peptide; PTHR, PTH/PTHrP receptor; PKA, protein kinase A; CREB, cAMP response element binding protein. e FGF signaling pathway: FGF signaling plays an important role during skeletal development and it controls endochondral and intramembranous ossification. FGF, fibroblast growth factor. f TGF-β/BMP signaling: TGF-β and BMP signaling are of utmost importance in both bone formation during skeletal development and maintenance of postnatal bone. TGF-β, transforming growth factor-β; BMPs, bone morphogenetic proteins; R-Smad, receptor-regulated Smad; co-Smad, common-mediator Smad