Osteopetrosis associated with PLEKHM1 and SNX10 genes, both involved in osteoclast vesicular trafficking

Huybrechts, Yentl; Hul, Wim

doi:10.1016/j.bone.2022.116520

Cited by 4 publications

(4 citation statements)

References 53 publications

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“…WNT3 also showed a Mendelian association with tetra-amelia syndrome 1 (#273395), and renal and adrenal agenesis have been observed in tetra-amelia syndrome 1 patients 41 . PLEKHM1 was involved in the biological process of metal ion binding and associated with osteopetrosis (#618107) 42 . Previous studies have shown elevated parathyroid hormones (PTH) in osteopetrosis patients 43,44 .…”

Section: Discussionmentioning

confidence: 99%

Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture

Hao,

Shao,

Zhang

et al. 2023

Nat Commun

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Kidney stone disease (KSD) is a complex disorder with high heritability and prevalence. We performed a large genome-wide association study (GWAS) meta-analysis for KSD to date, including 720,199 individuals with 17,969 cases in European population. We identified 44 susceptibility loci, including 28 novel loci. Cell type-specific analysis pinpointed the proximal tubule as the most relevant cells where susceptibility variants might act through a tissue-specific fashion. By integrating kidney-specific omics data, we prioritized 223 genes which strengthened the importance of ion homeostasis, including calcium and magnesium in stone formation, and suggested potential target drugs for the treatment. The genitourinary and digestive diseases showed stronger genetic correlations with KSD. In this study, we generate an atlas of candidate genes, tissue and cell types involved in the formation of KSD. In addition, we provide potential drug targets for KSD treatment and insights into shared regulation with other diseases.

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Section: Discussionmentioning

confidence: 99%

Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture

Hao,

Shao,

Zhang

et al. 2023

Nat Commun

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“…Cellular assays corroborated these findings; we observed that increased expression of SNX10 bolstered cell survival under stressful conditions, whereas its suppression compromised cellular resilience (Figure 4b). SNX10, part of the sorting nexin family, is involved in vesicular trafficking and cellular homeostasis (Chen et al, 2012;Huybrechts & Van Hul, 2022). Overexpression of exogenous SNX10 in cells leads to giant vacuoles formation (Qin et al, 2006), and its knockdown spurs cell growth and boosts glucose metabolism by triggering the mTORC1 pathway (Feng et al, 2023).…”

Section: Dmgs Function Inference From the Expression Assaysmentioning

confidence: 99%

Comparative DNA methylation reveals epigenetic adaptation to high altitude in snub-nosed monkeys

Wang,

Liu,

et al. 2024

Zoological Research

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DNA methylation has been proved to have a crucial role in environmental adaptations. Here, using whole-genome bisulfite sequencing method, we acquired the genome-wide DNA methylation profiles of Yunnan snub-nosed monkeys (Rhinopithecus bieti), which are known as the nonhuman primates that inhabit the highest altitude, and their close relatives, golden snub-nosed monkeys (R. roxellana). Overall, the DNA methylation levels had a trend towards slightly increased in golden snub-nosed monkeys compared with Yunnan snub-nosed monkeys, indicating a relatively more genome region are hypermethylated in the golden snub-nosed monkey. Comparative genomic methylation analysis found that genes associated with different methylated regions were involved in membrane fusion and vesicular formation and trafficking, hemoglobin, cell cycles regulation, and neuron differentiation. This result suggested that the high-altitude-related epigenetic modifications are comprehensive, involving a complete adaptation process from inhibiting single Ca 2+ channel protein to multiple proteins collaboratively enhancing vesicular function or inhibiting cell differentiation and proliferation. Further function assays have shown that overexpression or downregulation of candidate genes, such as SNX10, TIMELESS and CACYBP, affects cell viability under stress conditions. Our research indicates that comparing DNA methylation in similar species can provide new candidate genome regions/genes associated with local adaptations, thereby enhancing our understanding of how organisms adapt to their environments.

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“…Avb3 integrins, also known as vitronectin receptors, are present in the sealing zone's plasma membrane and help to tighten the connection to the underlying bone. Certain proteins in the bone matrix, like sialoprotein and osteopontin, include an amino acid pattern called "Arg-Gly-Asp (RGD)", with which this matrix receptor interacts [26]. A function for avb3 in resorption has been shown in in vivo investigations using RGD peptides and antibodies targeted against this complex.…”

Section: Osteoclast Functionmentioning

confidence: 99%

Carbonic Anhydrase II Activators in Osteopetrosis Treatment: A Review

Alkhayal

Shinwari

Gaafar

et al. 2023

CIMB

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Osteopetrosis is a rare hereditary illness generated by failure in osteoclasts resulting in elevated bone densities. Patients with osteopetrosis possess several complications, like dental caries, earlier teeth loss, delayed eruption, malformed crowns and roots, and lamina dura thickening. Since deficiency of carbonic anhydrase II is a major cause behind osteopetrosis, carbonic anhydrase II activators have a large number of applications in osteopetrosis treatment. There is a lack of a comprehensive review on osteopetrosis, pathogenesis of dental abnormalities, and the role of carbonic anhydrase II activators in osteopetrosis treatment. To address this research gap, the authros perfomed a comprehensive review on osteopetrosis and its types, pathogenesis of dental abnormalities, and the role of carbonic anhydrase II activators in osteopetrosis treatment. A brief introduction to the pathogenesis of dental abnormalities and regeneration is provided in this survey. A discussion of types of osteopetrosis depending on genetic inheritance, such as autosomal dominant, autosomal recessive, and X-linked inheritance osteopetrosis, is presented in this survey. The paper also focuses on the importance of carbonic anhydrase II activators as a potential drug therapy for dental osteopetrosis. In addition, a brief note on the role of azole and fluconazole in treating osteopetrosis is given. Finally, future directions involving gene therapy for dental osteopetrosis are described.

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Osteopetrosis associated with PLEKHM1 and SNX10 genes, both involved in osteoclast vesicular trafficking

Cited by 4 publications

References 53 publications

Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture

Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture

Comparative DNA methylation reveals epigenetic adaptation to high altitude in snub-nosed monkeys

Carbonic Anhydrase II Activators in Osteopetrosis Treatment: A Review

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