KIF22 regulates mitosis and proliferation of chondrocyte cells

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

iScience (Jul 2024)

KIF22 regulates mitosis and proliferation of chondrocyte cells

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

Affiliations

Hiroka Kawaue: Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan
Takuma Matsubara: Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan; Corresponding author
Kenichi Nagano: Department of Oral Pathology, Institute of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan
Aoi Ikedo: Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Toon, Ehime 791-0295, Japan
Thira Rojasawasthien: Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan
Anna Yoshimura: Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan
Chihiro Nakatomi: Division of Physiology, Department of Health Improvement, Kyushu Dental University, Manazuru, Kitakyushu, Fukuoka 803-8580, Japan
Yuuki Imai: Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Toon, Ehime 791-0295, Japan
Yoshimitsu Kakuta: Laboratory of Structural Biology, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Fukuoka 819-0395, Japan
William N. Addison: Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan
Shoichiro Kokabu: Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan; Corresponding author

Journal volume & issue: Vol. 27, no. 7
p. 110151

Abstract

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Summary: Point mutations in KIF22 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 Kif22 was highly expressed in proliferating-zone growth-plate chondrocytes. Kif22 knockdown resulted in defective mitotic spindle formation and reduced cell proliferation. Forced expression of SEMDJL-associated mutant Kif22 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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