Overexpression of Trpp5 contributes to cell proliferation and apoptosis probably through involving calcium homeostasis

Yan, Xiao; Lv, Xiaoyan; Cao, Ge; Bian, Guohui; Duan, Jingjing; Ai, Jianzhong; Sun, Huan; Li, Qingwei; Yang, Qiutan; Chen, Tielin; Zhao, Deqiang; Tan, Ruizhi; Liu, Yuhang; Wang, Yidong; Zhang, Zheng; Yang, Yang; Wei, Yuquan; Zhou, Qin

doi:10.1007/s11010-009-0379-8

Cited by 12 publications

(8 citation statements)

References 21 publications

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“…Dmp1-cKO -null primary osteoblasts exhibit increased cell proliferation and impaired osteoblast gene expression Xiao et al, 2011;Xiao, Y. et al, 2010;Xiao, Z. et al, 2010). Fourth, Kif3a…”

Section: Discussionmentioning

confidence: 99%

Disruption of Kif3a in osteoblasts results in defective bone formation and osteopenia

Qiu

Xiao

Cao

et al. 2012

Journal of Cell Science

104

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SummaryWe investigated whether Kif3a in osteoblasts has a direct role in regulating postnatal bone formation. We conditionally deleted Kif3a in osteoblasts by crossing osteocalcin (Oc; also known as Bglap)-Cre with Kif3a flox/null mice. Conditional Kif3a-null mice (Kif3a Oc-cKO ) had a 75% reduction in Kif3a transcripts in bone and osteoblasts. Conditional deletion of Kif3a resulted in the reduction of primary cilia number by 51% and length by 27% in osteoblasts. Kif3aOc-cKO mice developed osteopenia by 6 weeks of age unlike Kif3a flox/+ control mice, as evidenced by reductions in femoral bone mineral density (22%), trabecular bone volume (42%) and cortical thickness (17%). By contrast, Oc-Cre;Kif3a flox/+ and Kif3a flox/null heterozygous mice exhibited no skeletal abnormalities. Loss of bone mass in Kif3aOc-cKO mice was associated with impaired osteoblast function in vivo, as reflected by a 54% reduction in mineral apposition rate and decreased expression of Runx2, osterix (also known as Sp7 transcription factor 7; Sp7), osteocalcin and Dmp1 compared with controls. Immortalized osteoblasts from Kif3aOc-cKO mice exhibited increased cell proliferation, impaired osteoblastic differentiation, and enhanced adipogenesis in vitro. Osteoblasts derived from Kif3aOc-cKO mice also had lower basal cytosolic calcium levels and impaired intracellular calcium responses to fluid flow shear stress. Sonic hedgehog-mediated Gli2 expression and Wnt3a-mediated b-catenin and Axin2 expression were also attenuated in Kif3aOc-cKO bone and osteoblast cultures. These data indicate that selective deletion of Kif3a in osteoblasts disrupts primary cilia formation and/or function and impairs osteoblast-mediated bone formation through multiple pathways including intracellular calcium, hedgehog and Wnt signaling.

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“…Dmp1-cKO -null primary osteoblasts exhibit increased cell proliferation and impaired osteoblast gene expression Xiao et al, 2011;Xiao, Y. et al, 2010;Xiao, Z. et al, 2010). Fourth, Kif3a…”

Section: Discussionmentioning

confidence: 99%

Disruption of Kif3a in osteoblasts results in defective bone formation and osteopenia

Qiu

Xiao

Cao

et al. 2012

Journal of Cell Science

104

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“…It is unclear whether TRPP downregulation in MS lesions is beneficial or detrimental. On one hand, it may be detrimental because TRPP1 and TRPP3 channels are important for maintaining Ca 2+ homeostasis and contribute to cell proliferation (Xiao and Quarles, 2010 ; Xiao et al, 2010 ), while TRPP1 knockdown results in increased susceptibility to stress-induced cell death in kidney epithelial cells (Brill et al, 2020 ). On the other hand, overexpression of TRPP contributes to apoptosis (Xiao and Quarles, 2010 ; Xiao et al, 2010 ), and TRPP1 is upregulated as a direct consequence of ER and oxidative stress during pathological conditions.…”

Section: K + Channelsmentioning

confidence: 99%

Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

Boscia

Elkjaer

Illés

et al. 2021

Front. Cell. Neurosci.

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Despite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintaining white matter (WM) integrity and in regulating WM activities in axons, interstitial neurons, glia, and vascular cells. Recently, transcriptomic studies have considerably increased insight into the gene expression changes that occur in diverse WM lesions and the gene expression fingerprint of specific WM cells associated with secondary progressive MS. Here, we review the ion channel genes encoding K+, Ca2+, Na+, and Cl− channels; ryanodine receptors; TRP channels; and others that are significantly and uniquely dysregulated in active, chronic active, inactive, remyelinating WM lesions, and normal-appearing WM of secondary progressive MS brain, based on recently published bulk and single-nuclei RNA-sequencing datasets. We discuss the current state of knowledge about the corresponding ion channels and their implication in the MS brain or in experimental models of MS. This comprehensive review suggests that the intense upregulation of voltage-gated Na+ channel genes in WM lesions with ongoing tissue damage may reflect the imbalance of Na+ homeostasis that is observed in progressive MS brain, while the upregulation of a large number of voltage-gated K+ channel genes may be linked to a protective response to limit neuronal excitability. In addition, the altered chloride homeostasis, revealed by the significant downregulation of voltage-gated Cl− channels in MS lesions, may contribute to an altered inhibitory neurotransmission and increased excitability.

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“…The normal Pkd1 ϩ vs. cyclophilin A was normalized to the mean ratio of 5 control mice, which was set to 1. The percentage of conditionally deleted and mutant transcripts was calculated from the relative levels of the normal Pkd1 ϩ transcripts in different Pkd1 exons (73). All primer sequences of other genes used in real-time RT-PCR are provided in Table 1.…”

Section: Rna Isolation and Real-time Rt-pcrmentioning

confidence: 99%

Conditional deletion ofPkd1in osteocytes disrupts skeletal mechanosensing in mice

et al. 2011

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We investigated whether polycystin-1 is a bone mechanosensor. We conditionally deleted Pkd1 in mature osteoblasts/osteocytes by crossing Dmp1-Cre with Pkd1(flox/m1Bei) mice, in which the m1Bei allele is nonfunctional. We assessed in wild-type and Pkd1-deficient mice the response to mechanical loading in vivo by ulna loading and ex vivo by measuring the response of isolated osteoblasts to fluid shear stress. We found that conditional Pkd1 heterozygotes (Dmp1-Cre;Pkd1(flox/+)) and null mice (Pkd1(Dmp1-cKO)) exhibited a ∼ 40 and ∼ 90% decrease, respectively, in functional Pkd1 transcripts in bone. Femoral bone mineral density (12 vs. 27%), trabecular bone volume (32 vs. 48%), and cortical thickness (6 vs. 17%) were reduced proportionate to the reduction of Pkd1 gene dose, as were mineral apposition rate (MAR) and expression of Runx2-II, Osteocalcin, Dmp1, and Phex. Anabolic load-induced periosteal lamellar MAR (0.58 ± 0.14; Pkd1(Dmp1-cKO) vs. 1.68 ± 0.34 μm/d; control) and increases in Cox-2, c-Jun, Wnt10b, Axin2, and Runx2-II gene expression were significantly attenuated in Pkd1(Dmp1-cKO) mice compared with controls. Application of fluid shear stress to immortalized osteoblasts from Pkd1(null/null) and Pkd1(m1Bei/m1Bei)-derived osteoblasts failed to elicit the increments in cytosolic calcium observed in wild-type controls. These data indicate that polycystin-1 is essential for the anabolic response to skeletal loading in osteoblasts/osteocytes.

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Overexpression of Trpp5 contributes to cell proliferation and apoptosis probably through involving calcium homeostasis

Cited by 12 publications

References 21 publications

Disruption of Kif3a in osteoblasts results in defective bone formation and osteopenia

Disruption of Kif3a in osteoblasts results in defective bone formation and osteopenia

Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

Conditional deletion ofPkd1in osteocytes disrupts skeletal mechanosensing in mice

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