The period circadian clock 2 gene responds to glucocorticoids and regulates osteogenic capacity

Abe, Takahiro; Sato, Tomoya; Yoda, Tetsuya; Hoshi, Kazuto

doi:10.1016/j.reth.2019.07.006

Cited by 7 publications

(7 citation statements)

References 35 publications

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“…Honma et al [ 32 ] found that PER2 is a directly target gene of DEX. Abe et al [ 33 ] revealed that PER2 is required for the maturation of bone tissue. In this study, we suggested that PER2 directly regulating FGF2 through STITCH network.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of FGF2 delays the progression of osteonecrosis of the femoral head activating the PI3K/Akt signaling pathway

Shen

Ting

et al. 2021

J Orthop Surg Res

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Background The purpose of the current study was to explore the role and underlying mechanism of FGF-2 in dexamethasone (DEX)-induced apoptosis in MC3T3-E1 cells. Methods GSE21727 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. MC3T3-E1 cells were exposed to DEX at different concentrations (0, 10−8, 10−7, 10−6, 10−5 and 10−4 mol/L), and cell viability, flow cytometry and TUNEL assay were used to detect cell proliferation and apoptosis. An FGF-2-pcDNA3 plasmid (oe-FGF-2) was used to overexpress FGF-2, and western blotting was conducted to detect protein expression. Results We found that FGF-2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated FGF-2 gene and protein expression, inhibited viability and induced MC3T3-E1 cell apoptosis. Overexpression of FGF-2 reversed DEX-induced apoptosis in MC3T3-E1 cells. FGF-2-mediated anti-apoptosis was impaired by inactivating the PI3K/AKT pathway with LY294002. Moreover, overexpression of FGF2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model by regulation PI3K/Akt signaling pathway. Conclusion In conclusion, FGF-2 is effective at inhibiting DEX-induced MC3T3-E1 cell apoptosis through regulating PI3K/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Overexpression of FGF2 delays the progression of osteonecrosis of the femoral head activating the PI3K/Akt signaling pathway

Shen

Ting

et al. 2021

J Orthop Surg Res

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“…A single injection of dexamethasone could restore the circadian rhythm of osteoclast-related genes such as cathepsin K ( Ctsk ) in adrenalectomized mice ( 66 ). Per2 knock-out mice could not restore the GC-induced bone loss despite a bisphosphonate (Zoledronic acid) treatment, although Per2 knock-out osteoblasts showed an increased proliferation capacity ( 68 ).…”

Section: Circadian Rhythmicity and Gcsmentioning

confidence: 99%

Distinct Glucocorticoid Receptor Actions in Bone Homeostasis and Bone Diseases

et al. 2022

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Glucocorticoids (GCs) are steroid hormones that respond to stress and the circadian rhythm. Pharmacological GCs are widely used to treat autoimmune and chronic inflammatory diseases despite their adverse effects on bone after long-term therapy. GCs regulate bone homeostasis in a cell-type specific manner, affecting osteoblasts, osteoclasts, and osteocytes. Endogenous physiological and exogenous/excessive GCs act via nuclear receptors, mainly via the GC receptor (GR). Endogenous GCs have anabolic effects on bone mass regulation, while excessive or exogenous GCs can cause detrimental effects on bone. GC-induced osteoporosis (GIO) is a common adverse effect after GC therapy, which increases the risk of fractures. Exogenous GC treatment impairs osteoblastogenesis, survival of the osteoblasts/osteocytes and prolongs the longevity of osteoclasts. Under normal physiological conditions, endogenous GCs are regulated by the circadian rhythm and circadian genes display oscillatory rhythmicity in bone cells. However, exogenous GCs treatment disturbs the circadian rhythm. Recent evidence suggests that the disturbed circadian rhythm by continuous exogenous GCs treatment can in itself hamper bone integrity. GC signaling is also important for fracture healing and rheumatoid arthritis, where crosstalk among several cell types including macrophages and stromal cells is indispensable. This review summarizes the complexity of GC actions via GR in bone cells at cellular and molecular levels, including the effect on circadian rhythmicity, and outlines new therapeutic possibilities for the treatment of their adverse effects.

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“…19,26 Mutations in mice's CRY and PER genes led to increased osteoblast activity and bone mass. 33, 34 In addition to acting on osteoclasts, CRY2 is also crucial for the stability of the extracellular cartilage matrix. PER2 is vital for bone maturation, and the PER2 mutation promotes osteoblast proliferative activity.…”

Section: The Function Of Cry and Per In Osseointegrationmentioning

confidence: 99%

The Influence of Dental Implants on the Circadian Clock and the Role of Melatonin in the Oral Cavity

Škrlec¹

2022

Explor Res Hypothesis Med

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The circadian rhythm regulates many physiological human health and disease processes. The central circadian clock is located in the suprachiasmatic nucleus in the hypothalamus and controls a whole range of circadian clock genes. During bone remodeling, circadian rhythm gene expression was observed in osteoblasts and osteoclasts. Moreover, circadian rhythm genes are an essential part of the circadian network in the osseointegration of titanium implants. Namely, titanium biomaterials significantly affect the expression of the circadian clock gene in the oral cavity and thus regulate the establishment of osseointegration. In addition, vitamin D has potential practical implications for patients with dental implants because sufficient vitamin D levels before surgery improve the osseointegration process. Also, the hormone melatonin, whose production depending on the circadian rhythm, affects bone homeostasis. Therefore, melatonin affects bone formation and could serve as a regenerative agent by increasing the process of osseointegration. This review highlights the impact of dental implants on circadian rhythm and osseointegration.

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The period circadian clock 2 gene responds to glucocorticoids and regulates osteogenic capacity

Cited by 7 publications

References 35 publications

Overexpression of FGF2 delays the progression of osteonecrosis of the femoral head activating the PI3K/Akt signaling pathway

Overexpression of FGF2 delays the progression of osteonecrosis of the femoral head activating the PI3K/Akt signaling pathway

Distinct Glucocorticoid Receptor Actions in Bone Homeostasis and Bone Diseases

The Influence of Dental Implants on the Circadian Clock and the Role of Melatonin in the Oral Cavity

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