HSP90β promotes osteoclastogenesis by dual-activation of cholesterol synthesis and NF-κB signaling

Cheng, Huimin; Xing, Mingming; Zhou, Yaping; Zhang, Weitao; Liu, Zeyu; Li, Lan; Zheng, Zu-Guo; Ma, Yuanfang; Li, Ping Ping; Liu, Xiaoxuan; Li, Ping; Xu, Xiaojun

doi:10.1038/s41418-022-01071-3

Cited by 12 publications

(9 citation statements)

References 61 publications

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“…HSP90 has long been regarded as a housekeeping gene and serves as a loading control in several experiments. However, in our previous work, we found that HSP90β promoted de novo lipogenesis 9 , 37 . These studies indicated that HSP90β may exhibit paralog-specific roles in pathological conditions.…”

Section: Resultsmentioning

confidence: 69%

“…HSP90 facilitates the function of numerous proteins in cancer cells, and is often used as a loading control in WB assay. Evidence showing paralog-specific roles of HSP90β in diseases is emerging 9 , 37 . We found that HSP90β was positively correlated with disease progression, while the expression of HSP90α was not related to disease progression (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Sonic hedgehog-heat shock protein 90β axis promotes the development of nonalcoholic steatohepatitis in mice

Zhang,

Lu,

Feng

et al. 2024

Nat Commun

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Sonic hedgehog (SHH) and heat shock protein 90β (HSP90β) have been implicated in nonalcoholic steatohepatitis (NASH) but their molecular mechanisms of action remain elusive. We find that HSP90β is a key SHH downstream molecule for promoting NASH process. In hepatocytes, SHH reduces HSP90β ubiquitylation through deubiquitylase USP31, thus preventing HSP90β degradation and promoting hepatic lipid synthesis. HSP90β significantly increases in NASH mouse model, leading to secretion of exosomes enriched with miR-28-5p. miR-28-5p directly targetes and decreases Rap1b levels, which in turn promotes NF-κB transcriptional activity in macrophages and stimulates the expression of inflammatory factors. Genetic deletion, pharmacological inhibition of the SHH-HSP90β axis, or delivery of miR-28-5p to macrophages in the male mice liver, impairs NASH symptomatic development. Importantly, there is a markedly higher abundance of miR-28-5p in NASH patient sera. Taken together, the SHH-HSP90β-miR-28-5p axis offers promising therapeutic targets against NASH, and serum miR-28-5p may serve as a NASH diagnostic biomarker.

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Section: Resultsmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Sonic hedgehog-heat shock protein 90β axis promotes the development of nonalcoholic steatohepatitis in mice

Zhang,

Lu,

Feng

et al. 2024

Nat Commun

Self Cite

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“…These results are consistent with those reported previously. Both physiological and pathological remodeling of skeletal homeostasis are associated with NF-κB signaling, and the over-activation of NF-κB leads to osteoporosis and in ammatory bone loss [41,42]. In addition, NF-κB is involved in osteoclast activation.…”

Section: Discussionmentioning

confidence: 99%

TSG-6 inhibits the NF-κB signaling pathway and promotes the odontogenic differentiation of DPSCs via CD44 in an inflammatory environment

Wang,

Xie,

Xue

et al. 2024

Preprint

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In pulpitis, dentinal restorative processes are considerably associated with undifferentiated mesenchymal cells in the pulp. This study aimed to investigate strategies to improve the odonto/osteogenic differentiation of dental pulp stem cells (DPSCs) in an inflammatory environment. After pretreatment of DPSCs with 20 ng/mL tumor necrosis factor-induced protein-6 (TSG-6), DPSCs were cultured in an inflammation-inducing solution. Real-time polymerase chain reaction and western blotting were performed to measure the expression levels of nuclear factor kappa B (NF-κB) and odonto/osteogenic differentiation markers, respectively. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to assess cell proliferation and activity. Subcutaneous ectopic osteogenesis and mandibular bone cultures were performed to assess the effects of TSG-6 in vivo. The expression levels of odonto/osteogenic markers were higher in TSG-6-pre-treated DPSCs than nontreated DPSCs, whereas NF-κB-related proteins were lower after the induction of inflammation. An anti-CD44 antibody counteracted the rescue effect of TSG-6 on DPSC activity and mineralization in an inflammatory environment. Exogenous administration of TSG-6 enhanced the anti-inflammatory properties of DPSCs and partially restored their mineralization function by inhibiting NF-κB signaling. The mechanism of action of TSG-6 was attributed to its interaction with CD44. These findings reveal novel mechanisms by which DPSCs counter inflammation and provide a basis for the treatment of pulpitis.

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“…It is urgent for us to find new drug treatments and drug targets in conflict with obesity and pertinent metabolic disorders. In the last ten years, HSP90 has become a major therapeutic target for cancer [ 23 ], neurodegenerative disorders [ 24 ], anti-viral [ 25 ], and anti -osteoclastogenesis [ 26 ]. Although there are promising opportunities in utilizing HSP90 inhibitors for treating illnesses, the role of four paralogs from the HSP90 chaperone family in diseases is still not well comprehended.…”

Section: Discussionmentioning

confidence: 99%

Gkongensin A, an HSP90β inhibitor, improves hyperlipidemia, hepatic steatosis, and insulin resistance

Miao,

Zhao,

Xue

2024

Heliyon

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HSP90β promotes osteoclastogenesis by dual-activation of cholesterol synthesis and NF-κB signaling

Cited by 12 publications

References 61 publications

Sonic hedgehog-heat shock protein 90β axis promotes the development of nonalcoholic steatohepatitis in mice

Sonic hedgehog-heat shock protein 90β axis promotes the development of nonalcoholic steatohepatitis in mice

TSG-6 inhibits the NF-κB signaling pathway and promotes the odontogenic differentiation of DPSCs via CD44 in an inflammatory environment

Gkongensin A, an HSP90β inhibitor, improves hyperlipidemia, hepatic steatosis, and insulin resistance

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