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Review
. 2021 Mar 11;22(6):2851.
doi: 10.3390/ijms22062851.

Regulation of Osteoblast Differentiation by Cytokine Networks

Dulshara Sachini Amarasekara  1 , Sumi Kim  2 , Jaerang Rho  2
Affiliations
Review

Regulation of Osteoblast Differentiation by Cytokine Networks

Dulshara Sachini Amarasekara et al. Int J Mol Sci. .

Abstract

Osteoblasts, which are bone-forming cells, play pivotal roles in bone modeling and remodeling. Osteoblast differentiation, also known as osteoblastogenesis, is orchestrated by transcription factors, such as runt-related transcription factor 1/2, osterix, activating transcription factor 4, special AT-rich sequence-binding protein 2 and activator protein-1. Osteoblastogenesis is regulated by a network of cytokines under physiological and pathophysiological conditions. Osteoblastogenic cytokines, such as interleukin-10 (IL-10), IL-11, IL-18, interferon-γ (IFN-γ), cardiotrophin-1 and oncostatin M, promote osteoblastogenesis, whereas anti-osteoblastogenic cytokines, such as tumor necrosis factor-α (TNF-α), TNF-β, IL-1α, IL-4, IL-7, IL-12, IL-13, IL-23, IFN-α, IFN-β, leukemia inhibitory factor, cardiotrophin-like cytokine, and ciliary neurotrophic factor, downregulate osteoblastogenesis. Although there are gaps in the body of knowledge regarding the interplay of cytokine networks in osteoblastogenesis, cytokines appear to be potential therapeutic targets in bone-related diseases. Thus, in this study, we review and discuss our osteoblast, osteoblast differentiation, osteoblastogenesis, cytokines, signaling pathway of cytokine networks in osteoblastogenesis.

Keywords: cytokine; osteoblast; osteoblast differentiation; osteoblastogenesis; signaling pathway.

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Conflict of interest statement

The authors declare no potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of osteoblast (OB) differentiation. MSC, mesenchymal stem cell. BMP, bone morphogenetic protein. FGF, fibroblast growth factor. RUNX2, runt-related transcription factor 2. PTH, parathyroid hormone. TGF, transforming growth factor. Hh, hedgehog. SATB2, special AT-rich sequence-binding protein 2. OSX, osterix. ATF4, activating transcription factor 4. CREB, cAMP-responsive element-binding. ALP, alkaline phosphatase. OPN, osteopontin. OCN, osteocalcin. ONN, osteonectin. BSP, bone sialoprotein. COL1A1, collagen type 1 alpha 1 chain.
Figure 2
Figure 2
Key signaling pathways in osteoblastogenesis. BMP, bone morphogenetic protein. BMPR, BMP receptor. PTH, parathyroid hormone. PTH1R, PTH receptor 1. TGF-β, transforming growth factor-β. TGFβR, TGF-β receptor. FGF, fibroblast growth factor. FGFR, FGF receptor. Hh, hedgehog. PTCH1, patched 1. SMO, smoothened. RUNX1/2, runt-related transcription factor 1/2. OSX, osterix. ATF4, activating transcription factor 4. SATB2, special AT-rich sequence-binding protein 2. AP-1, activator protein-1. ROR, receptor tyrosine kinase-like orphan receptor. JNK, c-jun N-terminal kinase. CAMKII, calmodulin-dependent kinase II. PKC, protein kinase C. LRP, low-density lipoprotein receptor-related protein. APC, adenomatosis polyposis coli. CK1α, casein kinase 1α. GSK3β, glycogen synthase kinase 3β. cAMP, cyclic adenosine monophosphate. PKA, protein kinase A. CREB, cAMP-responsive element-binding. DLX5, distal-less homeobox 5. MAPK, mitogen-activated protein kinase. ERK, extracellular receptor kinase. PLC, phospholipase. AKT, protein kinase B. Gli, glioma-associated oncogene. Ub, Ubiquitin.
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