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. 2020 Oct 28;11:456. doi: 10.1186/s13287-020-01966-3

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — 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