%0 Journal Article
%T KIF22 regulates mitosis and proliferation of chondrocyte cells.
%A Kawaue H
%A Matsubara T
%A Nagano K
%A Ikedo A
%A Rojasawasthien T
%A Yoshimura A
%A Nakatomi C
%A Imai Y
%A Kakuta Y
%A Addison WN
%A Kokabu S
%J iScience
%V 27
%N 7
%D 2024 Jul 19
%M 38989461
%F 6.107
%R 10.1016/j.isci.2024.110151
%X 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.