Comparison of Kindlin-2 deficiency-stimulated osteoarthritis-like lesions induced by Prg4 versus Aggrecan transgene in mice

• DOI: 10.1016/j.jot.2023.05.005
• Publication Date: 2023-05-31T14:46:20Z
• Authors: Qing Yao; Weiyuan Gong; Xiaohao Wu; Donghao Gan; Chu Tao; Sixiong Lin; Minghao Qu; Zhongtian Ouyang; Mingjue Chen; Xinjia Hu; Guozhi Xiao
• Keywords: Aggrecan; Pathogenesis; SOX9

Genetically modified mice are the most useful tools for investigating gene functions in articular cartilage biology and pathogenesis of osteoarthritis. The AggrecanCreERT2 one reported mouse lines used this purpose. Prg4 (proteoglycan 4) encodes lubricin protein is expressed selectively chondrocytes located at superficial layer cartilage. While Prg4GFPCreERT2 knock-in inducible-Cre transgenic were generated a while ago, so far, few studies have line to perform functional biology.We recently that deleting Fermt2 gene, which key focal adhesion Kindlin-2, by using mice, results spontaneous osteoarthritis (OA) lesions, highly mimics human OA pathologies. In study, we compared Kindlin-2 deficiency-caused phenotypes induced with those caused imaging histological analyses.We find deleted about 75% tamoxifen (TAM)-treated Prg4GFPCreERt2/+; Fermt2fl/fl controls. At 6 months after TAM injections, OARSI scores AggrecanCreERT2/+; 5 3, respectively. knee joints osteophyte synovitis also significantly decreased Prg4GFPCreERT2/+; mice. Furthermore, magnitudes upregulation extracellular matrix-degrading enzymes Mmp13 hypertrophic chondrocyte markers Col10a1 Runx2 versus We finally examined susceptibility model surgically induce lesions. pathological features TAM-DMM exhibited significant enhancement erosion, proteoglycan loss, osteophyte, an increase score corn-oil DMM mice.Kindlin-2 loss causes milder OA-like lesions Prg4GFPCreERT2/+;Fermt2fl/fl than contrast, similarly accelerates destabilization medial meniscus-induced both mice.Translational Potential Article: Our study demonstrates tool research. This provides information investigators choose appropriate Cre their research biology.