17β-Estradiol on the Expression of G-Protein Coupled Estrogen Receptor (GPER/GPR30) Mitophagy, and the PI3K/Akt Signaling Pathway in ATDC5 Chondrocytes In Vitro

Fan, Dongxiao; Yang, Xiaonan; Li, Yinan; Guo, Lei

doi:10.12659/msm.909365

Cited by 48 publications

(42 citation statements)

References 64 publications

(64 reference statements)

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“…It is also important to note that chondrocytes are affected by many pathways, including the PI3K/Akt/Bcl pathway, which is involved in chondrocyte metabolism, growth, proliferation, survival, transcription, and protein synthesis . We supplemented the Western blot of the key protein PI3K, Akt, Bcl‐2 in this pathway, and the results are shown in Figure .…”

Section: Discussionmentioning

confidence: 99%

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

et al. 2019

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Problem: Osteoarthritis (OA) is a chronic disease with a very high incidence and the pathology of which is quite complex. Epidemiological investigation showed that OA may be related to smoking and estrogen levels, but there are few studies focused on the cross-effect of these two factors. This research aims to investigate the molecular mechanism of nicotine and estrogen effects on chondrocytes to study the effect of smoking on the incidence of osteoarthritis in women. Method of the study:Nicotine was added to obtain inflammatory supernatants of macrophages, which were used to induce chondrocyte inflammation. Toluidine staining and immunohistochemistry were used to detect the extracellular matrix (ECM) of chondrocytes, while the important proteins in the metabolism of chondrocytes were detected by Western blot. Results: Nicotine-induced inflammatory supernatant promoted the degradation of ECM, such as type II collagen, aggrecan and proteoglycan 4. While in the presence of physiological concentrations of estrogen, this destructive effect is reversed. On the molecular level, estrogen (17β-estradiol, 1 nmol/L) can inhibit the matrix degrading enzymes and promote the transforming growth factor (TGF)-β1 pathway which is involved in matrix synthesis. However, in the presence of inflammatory induction, although estrogen could still inhibit the expression of matrix degrading enzymes, it inhibited the TGF-β1 pathway. Moreover, the different inflammatory factors in the inflammatory supernatant, mainly tumor necrosis factor-α, interleukin-1β, had different effects on the metabolic processes of chondrocytes. Conclusion: Estrogen reverses nicotine-induced inflammation mainly via reducing the degradation of ECM. The cross-effect of estrogen and inflammatory factor inhibitors can be a potential clinical reference for OA patients. K E Y W O R D S chondrocytes, estrogen, extracellular matrix, nicotine, osteoarthritis | INTRODUC TI ONOsteoarthritis (OA) is one of the most common chronic, degenerative joint inflammations which can worldwide cause severe disabilities. 1 The pathology of this disease is very complex. Previous studies have found that estrogen is an important influencing factor that can inhibit the development of OA. 2 Recent studies also show that smoking has a certain impact on the occurrence of OA, but the specific mechanism is controversial. 3

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Section: Discussionmentioning

confidence: 99%

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

et al. 2019

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“…Another study indicated that knockout of PHF23 prevent the chondrocytes apoptosis against IL-1βinduced OA by increasing autophagy, mitophagy, collagen II expression and reducing the OA-related proteins, which might make PHF23 a possible therapeutic target for OA [142]. Fan et al [143] demonstrated that 17β-estradiol, a steroid hormone, inhibited mitophagy by activating the PI3K/AKT/ mTOR signaling pathway via the G-protein coupled estrogen receptor to exert protective effect on chondrocytes in OA. In addition, Blanco et al [144] indicated their hypothetic view on the key role of AMPK-SIRT-Parkin in regulating mitochondrial function and defensing against excessive ROS in the chondrocytes of OA ( Figure 6A).…”

Section: Oamentioning

confidence: 99%

The Role of Autophagy and Mitophagy in Bone Metabolic Disorders

et al. 2020

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Bone metabolic disorders include osteolysis, osteoporosis, osteoarthritis and rheumatoid arthritis. Osteoblasts and osteoclasts are two major types of cells in bone constituting homeostasis. The imbalance between bone formation by osteoblasts and bone resorption by osteoclasts has been shown to have a direct contribution to the onset of these diseases. Recent evidence indicates that autophagy and mitophagy, the selective autophagy of mitochondria, may play a vital role in regulating the proliferation, differentiation and function of osteoblasts and osteoclasts. Several signaling pathways, including PINK1/Parkin, SIRT1, MAPK8/FOXO3, Beclin-1/BECN1, p62/SQSTM1, and mTOR pathways, have been implied in the regulation of autophagy and mitophagy in these cells. Here we review the current progress about the regulation of autophagy and mitophagy in osteoblasts and osteoclasts in these bone metabolic disorders, as well as the molecular signaling activated or deactivated during this process. Together, we hope to draw attention to the role of autophagy and mitophagy in bone metabolic disorders, and their potential as a new target for the treatment of bone metabolic diseases and the requirements of further mechanism studies.

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“…Nonetheless and considering that 17β-E 2 was shown to induce GPR30 expression in ATDC5 mouse chondrogenic cells (Fan et al, 2018), it is also possible that GPR30 is only stably expressed…”

Section: Discussionmentioning

confidence: 99%

Expression and function of the nonclassical estrogen receptor, GPR30, in human cartilage and chondrocytes

Ribeiro

Sousa

Rufino

et al. 2020

Journal Cellular Physiology

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Estrogen hormones are important for cartilage homeostasis, but nothing is known regarding the expression and role of the membrane G protein‐coupled estrogen receptor (GPER), G protein‐coupled receptor 30 (GPR30), in adult articular chondrocytes. Using immunohistochemistry of cartilage sections, quantitative real‐time polymerase chain reaction and Western blot of chondrocyte extracts, we found that these cells express GPR30. Nonetheless, the pattern of bands detected by two distinct antibodies does not overlap, suggesting that the proteins detected represent partially degraded forms of the receptor. Treatment with GPR30 agonists did not induce Akt or ERK1/2 phosphorylation, two known GPR30‐activated signaling pathways, suggesting that GPR30 is not functional in human chondrocytes. Therefore, the protective anti‐osteoarthritic role of estrogen hormones in cartilage homeostasis is likely independent of GPR30. This study was performed using human cartilage collected from the distal femoral condyles of multiorgan donors at the Bone and Tissue Bank of the University and Hospital Center of Coimbra.

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17β-Estradiol on the Expression of G-Protein Coupled Estrogen Receptor (GPER/GPR30) Mitophagy, and the PI3K/Akt Signaling Pathway in ATDC5 Chondrocytes In Vitro

Cited by 48 publications

References 64 publications

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

The Role of Autophagy and Mitophagy in Bone Metabolic Disorders

Expression and function of the nonclassical estrogen receptor, GPR30, in human cartilage and chondrocytes

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