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Table 1 Factors involved in the regulation of osteogenesis and adipogenesis by excess GC

From: The shift in the balance between osteoblastogenesis and adipogenesis of mesenchymal stem cells mediated by glucocorticoid receptor

Factors

Species

Cell type

In vitro/in vivo study

Molecular mechanism

Ref(s)

Signaling pathways

 Wnt/β-catenin signaling

Human

Rat, mice

Osteoblasts

BM-MSCs

MC3T3-E1 cells

In vitro

In vitro, in vivo

Enhance Wnt signaling pathway inhibitors (such as DKK1, SFRPs, Wif1, and sclerostin); downregulate Wnt7b and Wnt10

[67,68,69,70,71,72]

 TGFβ/BMP superfamily

Mice

MC3T3-E1 cells

In vitro

Suppress BMP2; enhance BMP2 antagonists (follistatin and Dan)

[73, 74]

 Notch signaling

Mice

MC3T3-E1 cells

In vitro

In vivo

Enhance Notch1 and Notch 2; downregulate Notch target genes (such as Hey1, Hey2, and HeyL)

[75, 76]

Transcription factors/post-transcriptional regulators

 Runx2

Rat

Osteoblast

BM-MSCs

In vitro

In vitro

Inhibit Runx2; over-expression of Runx2 antagonizes GC-induced adipogenesis

[77,78,79]

 PPARγ and C/EBPs

Mice

Human

BM-MSCs

3T3-L1 preadipocytes

BM-MSCs

In vitro

In vitro

In vitro

Enhance PPARγ and C/EBP members (C/EBPα, β, and δ); Downregulate C/EBPβ in the later stage of the adipogenesis process

[16, 80,81,82]

 TAZ

Rat

Mice

BM-MSCs

3T3-L1 preadipocytes

In vitro

In vitro

Inhibit TAZ and ALP; overexpression of TAZ suppresses adipogenesis and promotes the trans-differentiation of preadipocytes into osteocytes

[83, 84]

 GILZ

Mice

Mice

BM-MSCs

3T3-L1 preadipocytes

In vitro

In vivo

Activate GILZ; overexpression of GILZ enhances osteogenesis, inhibits adipogenesis by inhibiting PPARγ2 and C/EBPα, and GILZ inhibits PPAR-γ2 mediated by C/EBP-δ

[85,86,87,88]

 Prostaglandin E2

Human

BM-MSCs

In vitro

Induce prostaglandin receptors to inhibit osteogenesis and enhance adipogenesis

[89]

MicroRNAs’ detailed information is shown in Table 2

 Long non-coding RNAs

Rat

Human

BM-MSCs

BM-MSCs

In vitro

In vitro

Downregulate lncRNA TCONS_00041960 and lncRNA RP11-154D6; lncRNA TCONS_00041960 enhances osteogenesis and inhibits adipogenesis by targeting miR-204-5p and miR125a-3p

[96, 97]

Other regulators

 Oxidative stress

Mice

Rat

Osteoblasts

Osteoblasts

In vitro

In vitro

Increase ROS to decrease Cbfa1 expression; N-acetylcysteine mitigates the detrimental effects of GC-induced oxidative stress

[98, 99]

 FilGAP–FLNA

Human

BM-MSCs

In vitro

Antagonize mechanical forces; FLNA and c-Tubulin play an important role in mechanical regulation during osteogenesis and adipogenesis

[100, 101]

  1. Factors, signaling pathways, transcription factors and post-transcriptional regulators, and other regulators, involved in the regulation of osteogenesis and adipogenesis by GC excess; Species, species involved in study; Cell type, cell type involved in the study; In vitro/In vivo Study, study performed in vitro or in vivo; Molecular mechanism, molecular mechanism involved in the regulation of osteogenesis or adipogenesis by excess GC; References, references related to the study in this table