Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice

Takami, Kenji; Okamoto, Kazuki; Etani, Yuki; Hirao, Makoto; Miyama, Akira; Okamura, Gensuke; Goshima, Atsushi; Miura, Taihei; Kurihara, Takuya; Fukuda, Yuji; Kanamoto, Takashi; Nakata, Ken; Okada, Seiji; Ebina, Kosuke

doi:10.1172/jci.insight.171962

Cited by 3 publications

(1 citation statement)

References 68 publications

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“… 343 However, teriparatide increases both bone formation and bone resorption, which results in reduced cortical bone volume and thickness, particularly in long bones with greater proportions of cortical bone. 341 , 344 A phase 4 clinical trial showed that 1 year of teriparatide treatment did not significantly reduce bone erosion in RA patients (NCT01400516). 345 In addition, due to the risk of osteosarcoma, teriparatide use is limited to those at a very high risk of fracture.…”

Section: Targeted Therapies For Skeletal Diseasesmentioning

confidence: 99%

Regulation of bone homeostasis: signaling pathways and therapeutic targets

Wu,

Li,

Jiang

et al. 2024

MedComm

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As a highly dynamic tissue, bone is continuously rebuilt throughout life. Both bone formation by osteoblasts and bone resorption by osteoclasts constitute bone reconstruction homeostasis. The equilibrium of bone homeostasis is governed by many complicated signaling pathways that weave together to form an intricate network. These pathways coordinate the meticulous processes of bone formation and resorption, ensuring the structural integrity and dynamic vitality of the skeletal system. Dysregulation of the bone homeostatic regulatory signaling network contributes to the development and progression of many skeletal diseases. Significantly, imbalanced bone homeostasis further disrupts the signaling network and triggers a cascade reaction that exacerbates disease progression and engenders a deleterious cycle. Here, we summarize the influence of signaling pathways on bone homeostasis, elucidating the interplay and crosstalk among them. Additionally, we review the mechanisms underpinning bone homeostatic imbalances across diverse disease landscapes, highlighting current and prospective therapeutic targets and clinical drugs. We hope that this review will contribute to a holistic understanding of the signaling pathways and molecular mechanisms sustaining bone homeostasis, which are promising to contribute to further research on bone homeostasis and shed light on the development of targeted drugs.

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Section: Targeted Therapies For Skeletal Diseasesmentioning

confidence: 99%

Regulation of bone homeostasis: signaling pathways and therapeutic targets

Wu,

Li,

Jiang

et al. 2024

MedComm

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Blood and Bone-Derived DNA Methylation Ages Predict Mortality After Geriatric Hip Fracture

Tarpada,

Heid,

Sun

et al. 2024

Journal of Bone and Joint Surgery

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Background: The purpose of this study was to (1) perform the first analysis of bone-derived DNA methylation, (2) compare DNA methylation clocks derived from bone with those derived from whole blood, and (3) establish a relationship between DNA methylation age and 1-year mortality within the geriatric hip fracture population. Methods: Patients ≥65 years old who presented to a Level-I trauma center with a hip fracture were prospectively enrolled from 2020 to 2021. Preoperative whole blood and intraoperative bone samples were collected. Following DNA extraction, RRBS (reduced representation bisulfite sequencing) libraries for methylation clock analysis were prepared. Sequencing data were analyzed using computational algorithms previously described by Horvath et al. to build a regression model of methylation (biological) age for each tissue type. Student t tests were used to analyze differences (Δ) in methylation age versus chronological age. Correlation between blood and bone methylation ages was expressed using the Pearson R coefficient. Results: Blood and bone samples were collected from 47 patients. DNA extraction, sequencing, and methylation analysis were performed on 24 specimens from 12 subjects. Mean age at presentation was 85.4 ± 8.65 years. There was no difference in DNA extraction yield between the blood and bone samples (p = 0.935). The mean follow-up duration was 12.4 ± 4.3 months. The mortality cohort (4 patients, 33%) showed a mean ΔAgeBone of 18.33 ± 6.47 years and mean ΔAgeBlood of 16.93 ± 4.02 years. In comparison, the survival cohort showed a significantly lower mean ΔAgeBone and ΔAgeBlood (7.86 ± 6.7 and 7.31 ± 7.71 years; p = 0.026 and 0.039, respectively). Bone-derived methylation age was strongly correlated with blood-derived methylation age (R = 0.81; p = 0.0016). Conclusions: Bone-derived DNA methylation clocks were found to be both feasible and strongly correlated with those derived from whole blood within a geriatric hip fracture population. Mortality was independently associated with the DNA methylation age, and that age was approximately 17 years greater than chronological age in the mortality cohort. The results of the present study suggest that prevention of advanced DNA methylation may play a key role in decreasing mortality following hip fracture. Level of Evidence: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

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Irisin: A Multifaceted Hormone Bridging Exercise and Disease Pathophysiology

Paoletti,

Coccurello

2024

IJMS

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The fibronectin domain-containing protein 5 (FNDC5), or irisin, is an adipo-myokine hormone produced during exercise, which shows therapeutic potential for conditions like metabolic disorders, osteoporosis, sarcopenia, obesity, type 2 diabetes, and neurodegenerative diseases, including Alzheimer’s disease (AD). This review explores its potential across various pathophysiological processes that are often considered independent. Elevated in healthy states but reduced in diseases, irisin improves muscle–adipose communication, insulin sensitivity, and metabolic balance by enhancing mitochondrial function and reducing oxidative stress. It promotes osteogenesis and mitigates bone loss in osteoporosis and sarcopenia. Irisin exhibits anti-inflammatory effects by inhibiting NF-κB signaling and countering insulin resistance. In the brain, it reduces amyloid-β toxicity, inflammation, and oxidative stress, enhancing brain-derived neurotrophic factor (BDNF) signaling, which improves cognition and synaptic health in AD models. It also regulates dopamine pathways, potentially alleviating neuropsychiatric symptoms like depression and apathy. By linking physical activity to systemic health, irisin emphasizes its role in the muscle–bone–brain axis. Its multifaceted benefits highlight its potential as a therapeutic target for AD and related disorders, with applications in prevention, in treatment, and as a complement to exercise strategies.

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Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice

Cited by 3 publications

References 68 publications

Regulation of bone homeostasis: signaling pathways and therapeutic targets

Regulation of bone homeostasis: signaling pathways and therapeutic targets

Blood and Bone-Derived DNA Methylation Ages Predict Mortality After Geriatric Hip Fracture

Irisin: A Multifaceted Hormone Bridging Exercise and Disease Pathophysiology

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