Norepinephrine modulates IL-1β-induced catabolic response of human chondrocytes

Hwang, Hyun Sook; Lee, Mi Hyun; Go, Dong Jin; Kim, Hyun Ah

doi:10.1186/s12891-021-04598-7

Cited by 11 publications

(5 citation statements)

References 38 publications

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“…Previous studies have reported that IL-1β promotes the secretion of pro-inflammatory mediators and accelerates OA progression [ 32 ]. Therefore, many studies use IL-1β as the major stimulator for OA [ 33 – 35 ]. Herein, IL-1β was also employed to establish in vitro OA model.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-specific peptidase 25 exacerbated osteoarthritis progression through facilitating TXNIP ubiquitination and NLRP3 inflammasome activation

Sui,

Dai,

Shi

et al. 2023

J Orthop Surg Res

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Several members of the ubiquitin-specific proteases (USPs) family have been revealed to regulate the progression of osteoarthritis (OA). The current study aimed to investigate the role and the underlying mechanism of USP25 in IL-1β-induced chondrocytes and OA rat model. It was discovered that IL-1β stimulation upregulated USP25, increased ROS level, and suppressed cell viability in rat chondrocytes. Besides, USP25 knockdown alleviated IL-1β-induced injury by decreasing ROS level, attenuating pyroptosis, and downregulating the expression of IL-18, NLRP3, GSDMD-N, active caspase-1, MMP-3, and MMP-13. Furthermore, we discovered that USP25 affected the IL-1β-induced injury in chondrocytes in a ROS-dependent manner. Moreover, USP25 was revealed to interact with TXNIP, and USP25 knockdown increased the ubiquitination of TXNIP. The pro-OA effect of USP25 abundance could be overturned by TXNIP suppression in IL-1β-induced chondrocytes. Finally, in vivo experiment results showed that USP25 inhibition alleviated cartilage destruction in OA rats. In conclusion, we demonstrated that USP25 stimulated the overproduction of ROS to activate the NLRP3 inflammasome via regulating TXNIP, resulting in increased pyroptosis and inflammation in OA.

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Section: Discussionmentioning

confidence: 99%

Ubiquitin-specific peptidase 25 exacerbated osteoarthritis progression through facilitating TXNIP ubiquitination and NLRP3 inflammasome activation

Sui,

Dai,

Shi

et al. 2023

J Orthop Surg Res

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“…Thus, elevated blood levels of NE most likely lead to defective bones via dysregulated adrenergic signaling in bones [17,40,41]. β2-adrenergic receptor-mediated signaling in response to the elevated NE inhibits bone formation and triggers RANKL-mediated osteoclastogenesis, thus increasing bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Intermittent Hypoxia in Neonatal Rodents Affects Facial Bone Growth

Pae

Harper

2023

Preprint

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Preterm human infants often show periodic breathing (PB) or apnea of prematurity (AOP), breathing patterns which are accompanied by intermittent hypoxia (IH). We examined cause-effect relationships between transient IH and reduced facial bone growth using a rat model. Neonatal pups from 14 timed pregnant Sprague-Dawley rats were randomly assigned to an IH condition, with oxygen altering between 10% and 21% every 4 min for 1 h immediately after birth, or to a litter-matched control group. The IH pups were compared with their age- and sex-matched control groups in body weight (WT), size of facial bones and nor-epinephrine (NE) levels in blood at 3, 4, and 5-weeks. Markedly increased activity of osteoclasts in sub-condylar regions of 3-week-old IH-treated animals appeared, as well as increased numbers of sympathetic nerve endings in the same region of tissue sections. Male IH-pups showed significantly higher levels of NE levels in sera at 3, 4 as well as 5-week-old time points. NE levels in 4- and-5-weekold female pups did not differ significantly. Intercondylar Width, Mandible Length and Intermolar Width measures consistently declined after IH insults in 3- and 4-week-old male as well as female animals. Three-week-old male IH-pups only showed a significantly reduced (p < 0.05) body weight compared to those of 3-week controls. However, female IH-pups were heavier than age-matched controls at all 3 time-points. Trabecular bone configuration, size of facial bones, and metabolism are disturbed after an IH challenge 1 h immediately after birth. The findings raise the possibility that IH, introduced by breathing patterns such as PB or AOP, induce significantly impaired bone development and metabolic changes in human newborns. The enhanced NE outflow from IH exposure may serve a major role in deficient bone growth, and may affect bone and other tissue influenced by that elevation.

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“…Our findings indicate that ‘IH stress’ elevates circulating NE levels, probably via an increased sympathetic transduction [ 40 , 41 ]. Thus, elevated blood levels of NE most likely lead to defective bones via dysregulated adrenergic signaling in bones [ 17 , 42 , 43 ]. β2-adrenergic receptor-mediated signaling in response to the elevated NE inhibits bone formation and triggers RANKL-mediated osteoclastogenesis, thus increasing bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Intermittent hypoxia in neonatal rodents affects facial bone growth

Pae,

Harper

2023

PLoS ONE

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Preterm human infants often show periodic breathing (PB) or apnea of prematurity (AOP), breathing patterns which are accompanied by intermittent hypoxia (IH). We examined cause-effect relationships between transient IH and reduced facial bone growth using a rat model. Neonatal pups from 14 timed pregnant Sprague-Dawley rats were randomly assigned to an IH condition, with oxygen altering between 10% and 21% every 4 min for 1 h immediately after birth, or to a litter-matched control group. The IH pups were compared with their age- and sex-matched control groups in body weight (WT), size of facial bones and nor-epinephrine (NE) levels in blood at 3, 4, and 5-weeks. Markedly increased activity of osteoclasts in sub-condylar regions of 3-week-old IH-treated animals appeared, as well as increased numbers of sympathetic nerve endings in the same region of tissue sections. Male IH-pups showed significantly higher levels of NE levels in sera at 3, 4 as well as 5-week-old time points. NE levels in 4- and-5-week-old female pups did not differ significantly. Intercondylar Width, Mandible Length and Intermolar Width measures consistently declined after IH insults in 3- and 4-week-old male as well as female animals. Three-week-old male IH-pups only showed a significantly reduced (p < 0.05) body weight compared to those of 3-week controls. However, female IH-pups were heavier than age-matched controls at all 3 time-points. Trabecular bone configuration, size of facial bones, and metabolism are disturbed after an IH challenge 1 h immediately after birth. The findings raise the possibility that IH, introduced by breathing patterns such as PB or AOP, induce significantly impaired bone development and metabolic changes in human newborns. The enhanced NE outflow from IH exposure may serve a major role in deficient bone growth, and may affect bone and other tissue influenced by that elevation.

show abstract

Norepinephrine modulates IL-1β-induced catabolic response of human chondrocytes

Cited by 11 publications

References 38 publications

Ubiquitin-specific peptidase 25 exacerbated osteoarthritis progression through facilitating TXNIP ubiquitination and NLRP3 inflammasome activation

Ubiquitin-specific peptidase 25 exacerbated osteoarthritis progression through facilitating TXNIP ubiquitination and NLRP3 inflammasome activation

Intermittent Hypoxia in Neonatal Rodents Affects Facial Bone Growth

Intermittent hypoxia in neonatal rodents affects facial bone growth

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