RRC ID 69870
Author Saito M, Hirano M, Izumi T, Mori Y, Ito K, Saitoh Y, Terada N, Sato T, Sukegawa J.
Title Cytoskeletal Protein 4.1G Is Essential for the Primary Ciliogenesis and Osteoblast Differentiation in Bone Formation.
Journal Int J Mol Sci
Abstract The primary cilium is a hair-like immotile organelle with specific membrane receptors, including the receptor of Hedgehog signaling, smoothened. The cilium organized in preosteoblasts promotes differentiation of the cells into osteoblasts (osteoblast differentiation) by mediating Hedgehog signaling to achieve bone formation. Notably, 4.1G is a plasma membrane-associated cytoskeletal protein that plays essential roles in various tissues, including the peripheral nervous system, testis, and retina. However, its function in the bone remains unexplored. In this study, we identified 4.1G expression in the bone. We found that, in the 4.1G-knockout mice, calcium deposits and primary cilium formation were suppressed in the trabecular bone, which is preosteoblast-rich region of the newborn tibia, indicating that 4.1G is a prerequisite for osteoblast differentiation by organizing the primary cilia in preosteoblasts. Next, we found that the primary cilium was elongated in the differentiating mouse preosteoblast cell line MC3T3-E1, whereas the knockdown of 4.1G suppressed its elongation. Moreover, 4.1G-knockdown suppressed the induction of the cilia-mediated Hedgehog signaling and subsequent osteoblast differentiation. These results demonstrate a new regulatory mechanism of 4.1G in bone formation that promotes the primary ciliogenesis in the differentiating preosteoblasts and induction of cilia-mediated osteoblast differentiation, resulting in bone formation at the newborn stage.
Volume 23(4)
Published 2022-2-14
DOI 10.3390/ijms23042094
PII ijms23042094
PMID 35216233
PMC PMC8878336
MeSH 3T3 Cells Animals Bone and Bones / metabolism Bone and Bones / physiology Calcification, Physiologic / physiology Cell Differentiation / physiology* Cell Line Cilia / metabolism* Cilia / physiology* Mice Mice, Knockout Microfilament Proteins / metabolism* Osteoblasts / metabolism* Osteoblasts / physiology* Osteogenesis / physiology* Signal Transduction / physiology
IF 4.556
Human and Animal Cells MC3T3-E1(RCB1126)