The role of primary cilia in cartilage development illustrated by the conditional knock out mouse model.
Gene
Function
IFT20
Col2-cre;Ift20fl/fl has normal limb development, but Prx-cre;Ift20fl/fl mouse shows four limb development defects. Deletion of Ift20 increased Fgf18 expression in the perichondrium that sustained Sox9 expression, thus preventing endochondral ossification [98]
IFT80
Deletion of IFT80 in the embryonic stage (injected tamoxifen at embryonic day 14.5 in Col2-creERT;IFT80 mouse) shows shortened cartilage and limbs at birth; deletion of IFT80 in the postnatal stage (injected tamoxifen at postnatal day 4 in Col2-creERT;IFT80 mouse) causes reduced growth plate length; loss of IFT80 blocks chondrocyte differentiation by disruption of ciliogenesis and alteration of Hh and Wnt signaling transduction, which in turn alters epiphyseal and articular cartilage formation [99]
IFT88
Col2-Cre;Ift88fl/fl mice display disorganized columnar structure and early loss of growth plate; Ift88 regulates the expression of Sfrp5 and Wnt signaling pathways in the growth plate via regulation of Ihh signaling [9] Aggrecan-CreERT;Ift88fl/fl mice have a thinner articular cartilage thickness in the middle of tibia at 33 weeks old [43]
KIF3a
Col2α1-Cre;Kif3afl/fl mice show postnatal dwarfism with a disorganized growth plate and altered chondrocyte orientation; deletion of Kif3a inhibits cell proliferation but accelerates hypertrophic differentiation, leading to the premature closure of the growth plate [100]
KIF5b
Col2α1-Cre;Kif5bfl/fl mice were smaller in stature owing to shortened spine vertebrae and long bones; mutant mice characterized by disorganized columnar structure in the growth plates; Kif5b mutation can cause incomplete cell rotation, proliferation, and differentiation disruption and results in a disorganized growth plate [101]