HIF-1α mediates osteoclast-induced disuse osteoporosis via cytoophidia in the femur of mice

Bie, Miaomiao; Tang, Yi; Xia, Yuxing; Zhang, Qian; Tian, Yuanye; Cheng, Chunan; Li, Xinzhao; Qi, Xin; Kang, Feiwu

doi:10.1016/j.bone.2022.116648

Cited by 5 publications

(1 citation statement)

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“…Thus, we speculate that Impdh2 also functions, potentially through cytoophidia, in other cell lineages derived from mesenchymal stem cells, e.g., adipocytes and osteoblasts. On the other hand, cytoplasmic Impdh-cytoophidia mediate HIF-1α signaling pathway regulation in disuse osteoporosis (Bie et al , 2023), and our study found that deletion of Impdh2 inhibits osteoclastogenesis via the impaired function of the mitochondrion and nuclear Impdh2-cytoophidia repress its transcriptional activity, indicating that Impdh2 regulates bone resorption by multifaceted regulatory mechanisms.…”

Section: Discussionmentioning

confidence: 57%

Nuclear cytoophidia assembly represses transcriptional activity to control skeletal development and homeostasis

Xu,

Wei,

et al. 2023

Preprint

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Compartmentation via filamentation is an evolutionarily conserved subcellular structure that fine-tunes the inherent activity of proteins. Cytoophidia represent a typical class of filamentous structures controlling enzymatic activities. Despite eukaryotic cells containing both cytoplasmic cytoophidia and nuclear cytoophidia, the physiological significance of nuclear cytoophidia is largely unknown. Here we show that nuclear filamentation inhibits the transcriptional activity of Impdh2 required for limb formation and bone resorption. Impdh2 deletion in mouse limb mesenchymal progenitors causes severe skeletal dysplasia by impairing endochondral ossification and chondrocyte differentiation. Additionally, Impdh2 deficiency in myeloid lineages leads to an increased bone mass via impeding osteoclast differentiation. Furthermore, Impdh2 regulates osteoclastic mitochondrial biogenesis and function. We propose that the nuclear compartmentalization of Impdh2 regulates the transcriptional activity during skeletal development and homeostasis.

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Section: Discussionmentioning

confidence: 57%