Effects of Androgen Receptor Overexpression on Chondrogenic Ability of Rabbit Articular Chondrocytes

Hui, Lisa; Shoumei, Xuan; Zhoujing, Zhang; Kuang, Gu; Zou, Duohong; He, Junguo; Zhou, Yong

doi:10.1007/s13770-021-00358-9

Cited by 5 publications

(4 citation statements)

References 22 publications

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“…Androgen receptor (AR) is a steroid hormone receptor that influences the transcription of androgen-responsive genes by binding their respective DNA sequences [ 87 ]. Moreover, AR can affect cell physiological activities, such as proliferation, apoptosis, and migration [ 88 ]. AR is expressed in human primary articular chondrocytes [ 89 ].…”

Section: Protective Effect Of Sex Hormones On Cartilage Degradationmentioning

confidence: 99%

“…Testosterone receptors have been discovered in rat chondrocytes from growth zone and resting zone cartilage in both sexes [ 90 ]. Additionally, in rabbits, AR overexpression has resulted in a reduced apoptosis rate and has maintained the phenotype of chondrocytes through inhibition of the mammalian target of rapamycin (mTOR) pathway to improve autophagy [ 88 ].…”

Section: Protective Effect Of Sex Hormones On Cartilage Degradationmentioning

confidence: 99%

“…Upregulated PI3K/AKT/mTOR in OA cartilage is linked to decreased expression of autophagy-related genes [ 158 ]. Overexpression of androgen has been shown to promote chondrogenesis and prevent degradation and apoptosis, potentially through mTOR-related signaling inhibition [ 88 ]. In addition, E2 inhibited autophagy upregulation to protect chondrocytes via the SIRT1-mediated AMPK/mTOR pathway [ 165 ].…”

Section: Molecular Mechanismsmentioning

confidence: 99%

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Sex-dependent variation in cartilage adaptation: from degeneration to regeneration

Patel

Chen²,

Katzmeyer

et al. 2023

Biol Sex Differ

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Despite acknowledgement in the scientific community of sex-based differences in cartilage biology, the implications for study design remain unclear, with many studies continuing to arbitrarily assign demographics. Clinically, it has been well-established that males and females differ in cartilage degeneration, and accumulating evidence points to the importance of sex differences in the field of cartilage repair. However, a comprehensive review of the mechanisms behind this trend and the influence of sex on cartilage regeneration has not yet been presented. This paper aims to summarize current findings regarding sex-dependent variation in knee anatomy, sex hormones’ effect on cartilage, and cartilaginous degeneration and regeneration, with a focus on stem cell therapies. Findings suggest that the stem cells themselves, as well as their surrounding microenvironment, contribute to sex-based differences. Accordingly, this paper underscores the contribution of both stem cell donor and recipient sex to sex-related differences in treatment efficacy. Cartilage regeneration is a field that needs more research to optimize strategies for better clinical results; taking sex into account could be a big factor in developing more effective and personalized treatments. The compilation of this information emphasizes the importance of investing further research in sex differences in cartilage biology.

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Section: Protective Effect Of Sex Hormones On Cartilage Degradationmentioning

confidence: 99%

Section: Protective Effect Of Sex Hormones On Cartilage Degradationmentioning

confidence: 99%

Section: Molecular Mechanismsmentioning

confidence: 99%

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Sex-dependent variation in cartilage adaptation: from degeneration to regeneration

Patel

Chen²,

Katzmeyer

et al. 2023

Biol Sex Differ

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“…Future investigation into the extent of bidirectional ER and EGFR cross-talk in chondrocytes and its influence on osteoarthritis would be justified. In addition to ERs, androgen receptor expression has been confirmed in rat growth plate chondrocytes and rabbit articular chondrocytes of both sexes, and overexpression can protect articular chondrocytes from apoptosis [ 22 , 40 ]. Furthermore, it has been shown that growth factor receptors, including EGFR, cross-talk with androgen receptor in prostate cancer and epithelial cells [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Sexual dimorphism in reactive oxygen species production and a role for integrin α1β1 in estrogen receptor α and β expression in articular cartilage

et al. 2023

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Background Osteoarthritis (OA) is a debilitating disease involving cartilage degradation. A need remains for the discovery of new molecular targets in cartilage for pharmaceutical intervention of OA. One potential target is integrin α1β1 that protects against OA when it is upregulated by chondrocytes early in the disease process. Integrin α1β1 offers this protection by dampening epidermal growth factor receptor (EGFR) signaling, and its effects are more robust in females compared to males. The aim of this study, therefore, was to measure the impact of itga1 on chondrocyte EGFR activity and downstream reactive oxygen species (ROS) production in male and female mice. Furthermore, chondrocyte expression of estrogen receptor (ER) α and ERβ was measured to investigate the mechanism for sexual dimorphism in the EGFR/integrin α1β1 signaling axis. We hypothesized that integrin α1β1 would decrease ROS production and pEGFR and 3-nitrotyrosine expression, with this effect being greater in females. We further hypothesized that chondrocyte expression of ERα and ERβ would be greater in females compared to males, with a greater effect seen in itga1-null compared to wild-type mice. Materials and methods Femoral and tibial cartilage of male and female, wild-type and itga1-null mice were processed for ex vivo confocal imaging of ROS, immunohistochemical analysis of 3-nitrotyrosine, or immunofluorescence of pEGFR and ERα and ERβ. Results We show that ROS-producing chondrocytes are more abundant in female itga1-null compared to wild-type mice ex vivo; however, itga1 had limited influence on the percent of chondrocytes stained positively for 3-nitrotyrosine or pEGFR in situ. In addition, we found that itga1 influenced ERα and ERβ expression in femoral cartilage from female mice, and that ERα and ERβ were coexpressed as well as colocalized in chondrocytes. Finally, we show sexual dimorphism in ROS and 3-nitrotyrosine production, but surprisingly not in pEGFR expression. Conclusions Together these data highlight sexual dimorphism in the EGFR/integrin α1β1 signaling axis and underline the need for further investigation into the role of ERs in this biological paradigm. Understanding the molecular mechanisms underlying the development of OA is essential for the development of individualized, sex-specific treatments in this age of personalized medicine.

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Effects of dynamic mechanical stimulations on the regeneration of in vitro and in vivo cartilage tissue based on silk fibroin scaffold

Fan

Zhou

et al. 2022

Composites Part B: Engineering

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Effects of Androgen Receptor Overexpression on Chondrogenic Ability of Rabbit Articular Chondrocytes

Cited by 5 publications

References 22 publications

Sex-dependent variation in cartilage adaptation: from degeneration to regeneration

Sex-dependent variation in cartilage adaptation: from degeneration to regeneration

Sexual dimorphism in reactive oxygen species production and a role for integrin α1β1 in estrogen receptor α and β expression in articular cartilage

Effects of dynamic mechanical stimulations on the regeneration of in vitro and in vivo cartilage tissue based on silk fibroin scaffold

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