驱动蛋白家族成员22（KIF22）调节软骨细胞的有丝分裂和增殖。

KIF22 regulates mitosis and proliferation of chondrocyte cells.

作者信息

Kawaue Hiroka, Matsubara Takuma, Nagano Kenichi, Ikedo Aoi, Rojasawasthien Thira, Yoshimura Anna, Nakatomi Chihiro, Imai Yuuki, Kakuta Yoshimitsu, Addison William N, Kokabu Shoichiro

机构信息

Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan.

Department of Oral Pathology, Institute of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.

出版信息

iScience. 2024 May 31;27(7):110151. doi: 10.1016/j.isci.2024.110151. eCollection 2024 Jul 19.

DOI:10.1016/j.isci.2024.110151

PMID:38989461

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11233920/

Abstract

Point mutations in have been linked to spondyloepimetaphyseal dysplasia with joint laxity, type 2 (SEMDJL2). Skeletal features of SEMDJL2 include short stature and joint laxity. Mechanisms underlying these limb abnormalities are unknown. Here in this manuscript, we have investigated the function of KIF22 in chondrocytes. Quantitative PCR and immunostaining revealed that was highly expressed in proliferating-zone growth-plate chondrocytes. knockdown resulted in defective mitotic spindle formation and reduced cell proliferation. Forced expression of SEMDJL-associated mutant constructs likewise induced abnormal mitotic spindle morphology and reduced proliferation. Mice expressing a KIF22 truncation mutant had shorter growth plates and shorter tibial bones compared to wild-type mice. These results suggest that KIF22 regulates mitotic spindle formation in proliferating chondrocytes thereby linking the stunted longitudinal bone growth observed in SEMDJL2 to failures of chondrocyte division.

摘要

的点突变与2型关节松弛型脊椎骨骺发育不良（SEMDJL2）有关。SEMDJL2的骨骼特征包括身材矮小和关节松弛。这些肢体异常的潜在机制尚不清楚。在本手稿中，我们研究了KIF22在软骨细胞中的功能。定量PCR和免疫染色显示，在增殖区生长板软骨细胞中高表达。敲低导致有丝分裂纺锤体形成缺陷和细胞增殖减少。SEMDJL相关突变体构建体的强制表达同样诱导了异常的有丝分裂纺锤体形态并减少了增殖。与野生型小鼠相比，表达KIF22截短突变体的小鼠生长板更短，胫骨更短。这些结果表明，KIF22调节增殖软骨细胞中的有丝分裂纺锤体形成，从而将SEMDJL2中观察到的纵向骨生长发育迟缓与软骨细胞分裂失败联系起来。