Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation

Shu, Bing; Zhao, Yongjian; Zhao, Shitian; Pan, Haobo; Xie, Rong; Yang, Junjie; Xue, Cong; Wang, Jing; Zhao, Dongfeng; Xiao, Guozhi; Wang, Yongjun; Chen, Di

doi:10.1038/s41413-020-0104-5

Cited by 23 publications

(12 citation statements)

References 41 publications

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“…Here, our study showed that deletion of BK channels in osteoblasts induced decreases in β-catenin expression in both bone tissues and primary osteoblasts. The inhibition of β-catenin in osteoblasts leads to an increase in osteoclast formation (Shu et al, 2020); however, trap staining in the trabecular regions showed no significant difference in our study. Runx2 is the main transcription factor in the process by which MSCs differentiate into osteoblasts.…”

Section: Discussioncontrasting

confidence: 87%

BK Channel Deficiency in Osteoblasts Reduces Bone Formation via the Wnt/β-Catenin Pathway

Jiang

Yang

Gao

et al. 2021

Molecules and Cells

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Global knockout of the BK channel has been proven to affect bone formation; however, whether it directly affects osteoblast differentiation and the mechanism are elusive. In the current study, we further investigated the role of BK channels in bone development and explored whether BK channels impacted the differentiation and proliferation of osteoblasts via the canonical Wnt signaling pathway. Our findings demonstrated that knockout of Kcnma1 disrupted the osteogenesis of osteoblasts and inhibited the stabilization of β-catenin. Western blot analysis showed that the protein levels of Axin1 and USP7 increased when Kcnma1 was deficient. Together, this study confirmed that BK ablation decreased bone mass via the Wnt/β-catenin signaling pathway. Our findings also showed that USP7 might have the ability to stabilize the activity of Axin1, which would increase the degradation of β-catenin in osteoblasts.

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Section: Discussioncontrasting

confidence: 87%

BK Channel Deficiency in Osteoblasts Reduces Bone Formation via the Wnt/β-Catenin Pathway

Jiang

Yang

Gao

et al. 2021

Molecules and Cells

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“…CSF-1, OPG, and AXIN1 are important for bone homeostasis, where CSF-1 is released by osteoblasts to directly induce osteoclastogenesis 81 . In contrast, OPG suppresses osteoclastogenesis, and its expression is upregulated by osteoblasts through β-catenin signalling 82 , which has recently been shown to be inhibited by AXIN1 83 . The exact mechanisms for the downregulation of these proteins, their interactions, and how they impact host response to PJI is unknown and warrants further study.…”

Section: Discussionmentioning

confidence: 99%

A 92 protein inflammation panel performed on sonicate fluid differentiates periprosthetic joint infection from non-infectious causes of arthroplasty failure

Fisher

Salmons

Mandrekar

et al. 2022

Sci Rep

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Periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty, typically necessitating surgical intervention and prolonged antimicrobial therapy. Currently, there is no perfect assay for PJI diagnosis. Proteomic profiling of sonicate fluid has the potential to differentiate PJI from non-infectious arthroplasty failure (NIAF) and possibly clinical subsets of PJI and/or NIAF. In this study, 200 sonicate fluid samples, including 90 from subjects with NIAF (23 aseptic loosening, 35 instability, 10 stiffness, five osteolysis, and 17 other) and 110 from subjects with PJI (40 Staphylococcus aureus, 40 Staphylococcus epidermidis, 10 Staphylococcus lugdunensis, 10 Streptococcus agalactiae, and 10 Enterococcus faecalis) were analyzed by proximity extension assay using the 92 protein Inflammation Panel from Olink Proteomics. Thirty-seven of the 92 proteins examined, including CCL20, OSM, EN-RAGE, IL8, and IL6, were differentially expressed in PJI versus NIAF sonicate fluid samples, with none of the 92 proteins differentially expressed between staphylococcal versus non-staphylococcal PJI, nor between the different types of NIAF studied. IL-17A and CCL11 were differentially expressed between PJI caused by different bacterial species, with IL-17A detected at higher levels in S. aureus compared to S. epidermidis and S. lugdunensis PJI, and CCL11 detected at higher levels in S. epidermidis compared to S. aureus and S. agalactiae PJI. Receiver operative characteristic curve analysis identified individual proteins and combinations of proteins that could differentiate PJI from NIAF. Overall, proteomic profiling using this small protein panel was able to differentiate between PJI and NIAF sonicate samples and provide a better understanding of the immune response during arthroplasty failure.

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“…In the fracture healing process, osteoclasts play an important role in the formation of new bones. In this process, the apoptosis of hypertrophic chondrocytes and resorption of the mineralized cartilage matrix by osteoclasts occurs, and is then replaced by new bone at the site of absorption 36 – 38 . Therefore, the active roles of both osteoblasts and osteoclasts are required for a successful fracture healing process.…”

Section: Discussionmentioning

confidence: 99%

Drug repositioning of polaprezinc for bone fracture healing

Park

Yoon

et al. 2022

Commun Biol

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Fractures and related complications are a common challenge in the field of skeletal tissue engineering. Vitamin D and calcium are the only broadly available medications for fracture healing, while zinc has been recognized as a nutritional supplement for healthy bones. Here, we aimed to use polaprezinc, an anti-ulcer drug and a chelate form of zinc and L-carnosine, as a supplement for fracture healing. Polaprezinc induced upregulation of osteogenesis-related genes and enhanced the osteogenic potential of human bone marrow-derived mesenchymal stem cells and osteoclast differentiation potential of mouse bone marrow-derived monocytes. In mouse experimental models with bone fractures, oral administration of polaprezinc accelerated fracture healing and maintained a high number of both osteoblasts and osteoclasts in the fracture areas. Collectively, polaprezinc promotes the fracture healing process efficiently by enhancing the activity of both osteoblasts and osteoclasts. Therefore, we suggest that drug repositioning of polaprezinc would be helpful for patients with fractures.

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Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation

Cited by 23 publications

References 41 publications

BK Channel Deficiency in Osteoblasts Reduces Bone Formation via the Wnt/β-Catenin Pathway

BK Channel Deficiency in Osteoblasts Reduces Bone Formation via the Wnt/β-Catenin Pathway

A 92 protein inflammation panel performed on sonicate fluid differentiates periprosthetic joint infection from non-infectious causes of arthroplasty failure

Drug repositioning of polaprezinc for bone fracture healing

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