Roles of Slit Ligands and Their Roundabout (Robo) Family of Receptors in Bone Remodeling

Niimi, Tomoaki

doi:10.1007/5584_2020_586

Cited by 6 publications

(3 citation statements)

References 69 publications

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“…The biological behavior of β-catenin after nuclear translocation in SCAP and the effect changes at the end of the signal pathway are still lack of exploration and veri cation of related experiments in this study, which will be a direction of follow-up research. In addition, SLIT3/ROBO can promote the proliferation and migration of osteoblasts by regulating the activity of cytoplasmic kinase Abl and then regulating the activity of downstream β-catenin 45 . So, is it possible for SLIT3 to mediate the change of β-catenin through Abl in SCAP, and then regulate the odontogenic differentiation?…”

Section: Discussionmentioning

confidence: 99%

SLIT3: a Novel Regulator of Odontogenic Differentiation through Akt/Wnt/β-catenin Signaling Pathway

Sun,

Jiang,

Liu

et al. 2024

Preprint

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The odontogenic differentiation of Stem cells from apical papilla (SCAP) is regulated by many extracellular matrix proteins, which plays a crucial role in dentin formation and regeneration. Extracellular matrix protein SLIT3, a classical axon guidance molecule, can link bone resorption to formation as clastokine. However, there is little information about SLIT3 in odontogenesis. Therefore, our study is aimed to explore the effects and possible mechanism of SLIT3 on the proliferation and differentiation of SCAP. Through Immunohistochemical staining and re-analysis of single-cell RNA sequencing and microarray datasets, we found that SLIT3 was expressed in the dental papilla and odontoblast layer of the developing molar tooth of mice. Real time polymerase chain reaction (RT-PCR) and Western blot assays also revealed an increased expression of SLIT3 during the odontogenic differentiation of SCAP. Afterwards, SLIT3 siRNA was used to knockdown SLIT3 and recombinant human SLIT3 (rhSLIT3) protein was used to treat SCAP. Cell Counting Kit-8 assays (CCK8) assays showed SLIT3 promoted proliferation of SCAP. Alkaline phosphatase (ALP) staining and Alizarin red staining were decreased/increased accordingly. Odontogenic markers DMP-1 and DSPP were also down-regulated/up-regulated. In addition, p-Akt and p-GSK3β levels were increased in rhSLIT3-treated SCAP and the movement into cell nucleus of β-catenin was promoted. The effect of SLIT3 was canceled after treatment with the inhibitor of Akt/Wnt/β-catenin signaling pathway. Taken together, our data show that SLIT3 could promote the proliferation and odontogenic differentiation of SCAP by activating Akt/Wnt/β-catenin signaling pathway.

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Section: Discussionmentioning

confidence: 99%

SLIT3: a Novel Regulator of Odontogenic Differentiation through Akt/Wnt/β-catenin Signaling Pathway

Sun,

Jiang,

Liu

et al. 2024

Preprint

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“…ROBO3 is a member of the ROBO protein family, a subfamily of the immunoglobulin transmembrane receptor superfamily ( Pak et al, 2020 ). ROBO proteins affect bone metabolism through Slit-ROBO signaling and neural epidermal growth factor-like proteins ( Niimi, 2021 ), as well as muscle patterning and vascular injury regulation ( Long and Van Vactor, 2012 ; Yuen and Robinson, 2013 ; Ordan and Volk, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis

et al. 2023

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Sarcopenia and osteoporosis, two degenerative diseases in older patients, have become severe health problems in aging societies. Muscles and bones, the most important components of the motor system, are derived from mesodermal and ectodermal mesenchymal stem cells. The adjacent anatomical relationship between them provides the basic conditions for mechanical and chemical signals, which may contribute to the co-occurrence of sarcopenia and osteoporosis. Identifying the potential common crosstalk genes between them may provide new insights for preventing and treating their development. In this study, DEG analysis, WGCNA, and machine learning algorithms were used to identify the key crosstalk genes of sarcopenia and osteoporosis; this was then validated using independent datasets and clinical samples. Finally, four crosstalk genes (ARHGEF10, PCDH7, CST6, and ROBO3) were identified, and mRNA expression and protein levels of PCDH7 in clinical samples from patients with sarcopenia, with osteoporosis, and with both sarcopenia and osteoporosis were found to be significantly higher than those from patients without sarcopenia or osteoporosis. PCDH7 seems to be a key gene related to the development of both sarcopenia and osteoporosis.

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“…Mice with an osteoblastspecific deletion of SHN3 demonstrated better bone formation and greater levels of CD31 hi Emcn hi ECs. 21,78 The above mentioned indicates that bone tissue engineering scaffolds that targeted the Slit3 pathway provided a new approach for regulating vascular-targeted bone metabolism.…”

Section: Notch Signaling Targeted Tissue Engineering Strategymentioning

confidence: 99%

Type H blood vessels in coupling angiogenesis‐osteogenesis and its application in bone tissue engineering

Kusumbe

Cai

et al. 2023

J Biomed Mater Res

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One specific capillary subtype, termed type H vessel, has been found with unique functional characteristics in coupling angiogenesis with osteogenesis. Researchers have fabricated a variety of tissue engineering scaffolds to enhance bone healing and regeneration through the accumulation of type H vessels. However, only a limited number of reviews discussed the tissue engineering strategies for type H vessel regulation. The object of this review is to summary the current utilizes of bone tissue engineering to regulate type H vessels through various signal pathways including Notch, PDGF-BB, Slit3, HIF-1α, and VEGF signaling. Moreover, we give an insightful overview of recent research progress about the morphological, spatial and agedependent characteristics of type H blood vessels. Their unique role in tying angiogenesis and osteogenesis together via blood flow, cellular microenvironment, immune system and nervous system are also summarized. This review article would provide an insight into the combination of tissue engineering scaffolds with type H vessels and identify future perspectives for vasculized tissue engineering research.

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Roles of Slit Ligands and Their Roundabout (Robo) Family of Receptors in Bone Remodeling

Cited by 6 publications

References 69 publications

SLIT3: a Novel Regulator of Odontogenic Differentiation through Akt/Wnt/β-catenin Signaling Pathway

SLIT3: a Novel Regulator of Odontogenic Differentiation through Akt/Wnt/β-catenin Signaling Pathway

PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis

Type H blood vessels in coupling angiogenesis‐osteogenesis and its application in bone tissue engineering

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