KIF22 regulates mitosis and proliferation of chondrocyte cells

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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.

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Highlights

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KIF22 facilitates chondrocyte proliferation by regulating mitosis
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Expression of KIF22 SEMDJL2 mutants cause defective cell proliferation in vitro
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KIF22 truncation mutant mice exhibit growth plate abnormalities

Abstract

Cell biology; Molecular biology.

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Most cited references 51

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Guidelines for assessment of bone microstructure in rodents using micro-computed tomography.

Mary Bouxsein, Stephen K Boyd, Blaine A Christiansen … (2010)

Use of high-resolution micro-computed tomography (microCT) imaging to assess trabecular and cortical bone morphology has grown immensely. There are several commercially available microCT systems, each with different approaches to image acquisition, evaluation, and reporting of outcomes. This lack of consistency makes it difficult to interpret reported results and to compare findings across different studies. This article addresses this critical need for standardized terminology and consistent reporting of parameters related to image acquisition and analysis, and key outcome assessments, particularly with respect to ex vivo analysis of rodent specimens. Thus the guidelines herein provide recommendations regarding (1) standardized terminology and units, (2) information to be included in describing the methods for a given experiment, and (3) a minimal set of outcome variables that should be reported. Whereas the specific research objective will determine the experimental design, these guidelines are intended to ensure accurate and consistent reporting of microCT-derived bone morphometry and density measurements. In particular, the methods section for papers that present microCT-based outcomes must include details of the following scan aspects: (1) image acquisition, including the scanning medium, X-ray tube potential, and voxel size, as well as clear descriptions of the size and location of the volume of interest and the method used to delineate trabecular and cortical bone regions, and (2) image processing, including the algorithms used for image filtration and the approach used for image segmentation. Morphometric analyses should be based on 3D algorithms that do not rely on assumptions about the underlying structure whenever possible. When reporting microCT results, the minimal set of variables that should be used to describe trabecular bone morphometry includes bone volume fraction and trabecular number, thickness, and separation. The minimal set of variables that should be used to describe cortical bone morphometry includes total cross-sectional area, cortical bone area, cortical bone area fraction, and cortical thickness. Other variables also may be appropriate depending on the research question and technical quality of the scan. Standard nomenclature, outlined in this article, should be followed for reporting of results. 2010 American Society for Bone and Mineral Research.

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David W. Dempster, Juliet Compston, Marc Drezner … (2013)

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Author and article information

Contributors

Takuma Matsubara

Shoichiro Kokabu

Journal

Journal ID (nlm-ta): iScience

Journal ID (iso-abbrev): iScience

Title: iScience

Publisher: Elsevier

ISSN (Electronic): 2589-0042

Publication date PMC-release: 31 May 2024

Publication date Collection: 19 July 2024

Publication date (Electronic): 31 May 2024

Volume: 27

Issue: 7

Electronic Location Identifier: 110151

Affiliations

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

[2 ]Department of Oral Pathology, Institute of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan

[3 ]Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Toon, Ehime 791-0295, Japan

[4 ]Division of Physiology, Department of Health Improvement, Kyushu Dental University, Manazuru, Kitakyushu, Fukuoka 803-8580, Japan

[5 ]Laboratory of Structural Biology, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Fukuoka 819-0395, Japan

Author notes

[∗ ]Corresponding author r15matsubara@ 123456fa.kyu-dent.ac.jp

[∗∗ ]Corresponding author r14kokabu@ 123456fa.kyu-dent.ac.jp

[6]

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Article

Publisher Item ID: S2589-0042(24)01376-2 Publisher ID: 110151

DOI: 10.1016/j.isci.2024.110151

PMC ID: 11233920

PubMed ID: 38989461

SO-VID: 0dbf2c86-737a-44c8-9852-42b193e4ad9b

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

History

Date received : 4 September 2023

Date revision received : 12 March 2024

Date accepted : 28 May 2024

KIF22 regulates mitosis and proliferation of chondrocyte cells

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Evolutionary Cell Biology

Most cited references 51

NIH Image to ImageJ: 25 years of image analysis

Guidelines for assessment of bone microstructure in rodents using micro-computed tomography.

Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee.

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