Estrogen receptor α in mature osteoblasts regulates the late stage of bone regeneration

Ikedo, Aoi; Imai, Yuuki

doi:10.1016/j.bbrc.2021.04.112

Cited by 5 publications

(4 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests that ligand-independent ERα signaling negatively regulates osteoblast formation and activity in the fracture callus of estrogen-deficient mice during bone regeneration. Regarding the role of ERα during fracture healing, to our knowledge, there is only one other study using mice with an ERα deletion in mature osteoblasts and osteocytes that uses a monocortical defect model on the tibiae of female mice ( Ikedo and Imai, 2021 ). In agreement with our findings, they also reported that the ERα on mature osteoblasts controls osteoblast number and osteoblast surface.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Receptor α Signaling in Osteoblasts is Required for Mechanotransduction in Bone Fracture Healing

Steppe¹,

Krüger²,

Tschaffon³

et al. 2021

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Biomechanical stimulation by whole-body low-magnitude high-frequency vibration (LMHFV) has demonstrated to provoke anabolic effects on bone metabolism in both non-osteoporotic and osteoporotic animals and humans. However, preclinical studies reported that vibration improved fracture healing and bone formation in osteoporotic, ovariectomized (OVX) mice representing an estrogen-deficient hormonal status, but impaired bone regeneration in skeletally healthy non-OVX mice. These effects were abolished in general estrogen receptor α (ERα)-knockout (KO) mice. However, it remains to be elucidated which cell types in the fracture callus are targeted by LMHFV during bone healing. To answer this question, we generated osteoblast lineage-specific ERα-KO mice that were subjected to ovariectomy, femur osteotomy and subsequent vibration. We found that the ERα specifically on osteoblastic lineage cells facilitated the vibration-induced effects on fracture healing, because in osteoblast lineage-specific ERα-KO (ERαfl/fl; Runx2Cre) mice the negative effects in non-OVX mice were abolished, whereas the positive effects of vibration in OVX mice were reversed. To gain greater mechanistic insights, the influence of vibration on murine and human osteogenic cells was investigated in vitro by whole genome array analysis and qPCR. The results suggested that particularly canonical WNT and Cox2/PGE2 signaling is involved in the mechanotransduction of LMHFV under estrogen-deficient conditions. In conclusion, our study demonstrates a critical role of the osteoblast lineage-specific ERα in LMHFV-induced effects on fracture healing and provides further insights into the molecular mechanism behind these effects.

show abstract

Section: Discussionmentioning

confidence: 99%

Estrogen Receptor α Signaling in Osteoblasts is Required for Mechanotransduction in Bone Fracture Healing

Steppe¹,

Krüger²,

Tschaffon³

et al. 2021

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…99 ERα, but not ERβ, in osteocalcin-positive osteoblasts was suggested to boost the late stage of bone regeneration in female mice. 190 Ovariectomy induces enhanced expression of microRNA-148a and osteoporosis, and microRNA-148a increases apoptosis of osteoblasts by inhibiting ERα in female mice. 191 …”

Section: Molecular Mechanisms Underlying Sexual Dimorphism In Osteopo...mentioning

confidence: 99%

Insights and implications of sexual dimorphism in osteoporosis

Zhang,

Xie,

Sun

et al. 2024

Bone Res

View full text Add to dashboard Cite

Osteoporosis, a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture, has led to a high risk of fatal osteoporotic fractures worldwide. Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis, with sex-specific differences in epidemiology and pathogenesis. Specifically, females are more susceptible than males to osteoporosis, while males are more prone to disability or death from the disease. To date, sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells. Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men. This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis, mainly in a population of aging patients, chronic glucocorticoid administration, and diabetes. Moreover, we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men. Additionally, the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.

show abstract

“…ERα deficiency was considered as one of the reasons for postmenopausal women’s high fracture rate [ 38 ]. In the fracture healing process, ERα deficiency may severely impair the interaction between osteoclasts and osteoblasts, and subsequently affected callus remodeling [ 39 ]. These findings indicated the significance of ERα in bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

Sesamin Promotes Osteoporotic Fracture Healing by Activating Chondrogenesis and Angiogenesis Pathways

Yang

Wang

et al. 2022

Nutrients

View full text Add to dashboard Cite

Osteoporotic fracture has been regarded as one of the most common bone disorders in the aging society. The natural herb-derived small molecules were revealed as potential treatment approaches for osteoporotic fracture healing. Sesamin is a member of lignan family, which possesses estrogenic activity and plays a significant role in modulating bone homeostasis. Our previous study reported the promoting effect of sesamin on postmenopausal osteoporosis treatment. However, the role of sesamin in osteoporotic fracture healing has not been well studied yet. In this study, we further investigated the putative treatment effect of sesamin on osteoporotic fracture healing. Our study indicated that sesamin could activate bone morphogenetic protein 2 (BMP2) signaling pathway and further promotes in vitro chondrogenesis and angiogenesis activities. This promoting effect was abolished by the treatment of ERα inhibitor. In the osteoporotic bone fracture model, we demonstrated that sesamin markedly improves the callus formation and increases the cartilaginous area at the early-stage, as well as narrowing the fracture gap, and expands callus volume at the late-stage fracture healing site of the OVX mice femur. Furthermore, the angiogenesis at the osteoporotic fracture site was also significantly improved by sesamin treatment. In conclusion, our research illustrated the therapeutic potential and underlying regulation mechanisms of sesamin on osteoporotic fracture healing. Our studies shed light on developing herb-derived bioactive compounds as novel drugs for the treatment of osteoporotic fracture healing, especially for postmenopausal women with low estrogen level.

show abstract

Estrogen receptor α in mature osteoblasts regulates the late stage of bone regeneration

Cited by 5 publications

References 24 publications

Estrogen Receptor α Signaling in Osteoblasts is Required for Mechanotransduction in Bone Fracture Healing

Estrogen Receptor α Signaling in Osteoblasts is Required for Mechanotransduction in Bone Fracture Healing

Insights and implications of sexual dimorphism in osteoporosis

Sesamin Promotes Osteoporotic Fracture Healing by Activating Chondrogenesis and Angiogenesis Pathways

Contact Info

Product

Resources

About