Puerarin specifically disrupts osteoclast activation via blocking integrin-β3 Pyk2/Src/Cbl signaling pathway

Qiu, Zuo-Cheng; Li, Ling; Huang, Yuying; Shi, Keda; Zhang, Lizhong; Huang, Cuishan; Liang, Jiechao; Zeng, Qing‐Yin; Wang, Jiali; He, Xiangjiu; Qin, Ling; Wang, Xinluan

doi:10.1016/j.jot.2022.01.003

Cited by 22 publications

(15 citation statements)

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“…After a series of washes, mechanical emulsification, and centrifugation, fresh fat tissue was converted to water-soluble, non-immunogenic CEFFE. Previous studies confirmed that hyperactive osteoclastogenesis is the leading cause of bone loss in OVX mice [1]. Therefore, to investigate the effect of CEFFE on osteoclastogenesis in vivo , OVX mouse models were established and treated with CEFFE twice per week ( Figure 1B ).…”

Section: Resultsmentioning

confidence: 95%

“…Hyperactive osteoclastogenesis causes unbalanced bone remodeling, which is a common feature of osteolytic bone diseases, such as osteoporosis, osteoarthritis, tumorous bone metastasis, and osteomyelitis [1][2][3]. Osteoporosis is a highly prevalent metabolic bone disease characterized by bone loss and deterioration of bone microarchitecture.…”

Section: Introductionmentioning

confidence: 99%

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Fat Extract Modulates Calcium Signaling and Protects Against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Yang¹,

Xu²,

Kan³

et al. 2022

Preprint

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Osteoclasts are cells which are primarily involved in bone remodeling and osteolytic bone diseases. Hyperactive osteoclastogenesis leads to pathological bone loss and microarchitectural deterioration, particularly in postmenopausal osteoporosis. However, given the limitations of current first-line osteoclast inhibitors, there is an urgent need for a novel antiresorptive agent with higher efficiency and fewer side effects. Cell-free fat extract (CEFFE) is the liquid fraction obtained from human adipose tissues, which are enriched with a variety of cytokines and growth factors. This study aims to explore its pharmacologic effect on hyperactive osteoclast formation in vivo and in vitro. CEFFE exhibits excellent potentials to attenuate osteoclast-associated bone loss in an ovariectomy (OVX) mouse model and to inhibit RANKL-induced osteoclastogenesis in primary bone marrow-derived monocytes. Furthermore, the cationic protein fraction of CEFFE (CEFFE-Cation) is identified as the main inhibitory component in osteoclast formation assay. Excessive reactive oxygen species (ROS) production is the main cause of osteoclast overactivation. According to LC-MS/MS analysis, the CEFFE-Cation fraction mainly consists of various antioxidant enzymes, extracellular matrix, and adipokines, which endow it with a superior antioxidant capacity. Calcium signaling contributes to osteoclast maturation. In addition to scavenging ROS, CEFFE-Cation is also capable of mitigating calcium oscillaion, calcineurin activation, and subsequent NFATc1 nuclear translocation during osteoclastogenesis. Overall, this study elucidates the promising translational potential of CEFFE as a next-generation personalized antiresorptive agent for osteolytic bone disease treatment.

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Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Fat Extract Modulates Calcium Signaling and Protects Against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Yang¹,

Xu²,

Kan³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Although this correlation between gut microbiota and bone metabolism has been found, whether bone physiology can be targeted through microbiota intervention requires further exploration. There are still many new targets being explored, such as platelet-derived growth factor-BB (PDGF-BB) [ 115 ] secreted by pre-osteoclasts, sphingosine-1-phosphate lyase [ 116 ], and integrin-β3 signaling [ 117 ], as some new research strategies are needed to enter clinical research.…”

Section: The Regulation Of Bone Remodeling In Health and Osteoporosismentioning

confidence: 99%

Osteoporosis pathogenesis and treatment: existing and emerging avenues

et al. 2022

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Osteoporotic fractures lead to increased disability and mortality in the elderly population. With the rapid increase in the aging population around the globe, more effective treatments for osteoporosis and osteoporotic fractures are urgently required. The underlying molecular mechanisms of osteoporosis are believed to be due to the increased activity of osteoclasts, decreased activity of osteoblasts, or both, which leads to an imbalance in the bone remodeling process with accelerated bone resorption and attenuated bone formation. Currently, the available clinical treatments for osteoporosis have mostly focused on factors influencing bone remodeling; however, they have their own limitations and side effects. Recently, cytokine immunotherapy, gene therapy, and stem cell therapy have become new approaches for the treatment of various diseases. This article reviews the latest research on bone remodeling mechanisms, as well as how this underpins current and potential novel treatments for osteoporosis.

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“…The radiographic features include bone rarefaction, decreased bone mass, disruption of trabecular continuity. The occurrence and development of osteoporosis are closely related to osteoclasts, so the key for treatment of osteoporosis is to focus primarily on inhibiting osteoclast differentiation and inducing osteoclast apoptosis ( Tan et al, 2017 ; Da et al, 2021 ; Qiu et al, 2022 ; Wang et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

How zoledronic acid improves osteoporosis by acting on osteoclasts

et al. 2022

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Osteoporosis is called a silent disease, because it is difficult to detect until comprehensive examinations for osteoporosis are performed or osteoporotic fractures occur. Zoledronic acid is currently the first-line anti-osteoporotic drug, with good efficacy and treatment compliance. A major advantage of zoledronic acid is that intravenous zoledronic acid often guarantees a therapeutic effect for up to 1 year after infusion. The reasons why zoledronic acid is effective in improving osteoporosis are that it can inhibit osteoclast differentiation and induce osteoclast apoptosis, thus suppressing bone resorption and increasing bone density. The story between zoledronic acid and osteoclasts has been written long time ago. Both the canonical receptor activator of the receptor activator of nuclear factor-κB ligand (RANKL) pathway and the non-canonical Wnt pathway are the main pathways by which zoledronic acid inhibits osteoclast differentiation. Farnesyl pyrophosphate synthase (FPPS), reactive oxygen species (ROS), and ferroptosis that was first proposed in 2012, are all considered to be closely associated with zoledronic acid-induced osteoclast apoptosis. Here, we provide a brief review of the recent progress on the study of zoledronic acid and osteoclasts, and hope to elaborate how zoledronic acid improves osteoporosis by acting on osteoclasts.

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Puerarin specifically disrupts osteoclast activation via blocking integrin-β3 Pyk2/Src/Cbl signaling pathway

Cited by 22 publications

References 50 publications

Fat Extract Modulates Calcium Signaling and Protects Against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Fat Extract Modulates Calcium Signaling and Protects Against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Osteoporosis pathogenesis and treatment: existing and emerging avenues

How zoledronic acid improves osteoporosis by acting on osteoclasts

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