Kdm7a, also known as Lysine-specific demethylase 7A, KIAA1718 or JHDM1D, is an α-ketoglutarate-and Fe(II)-dependent histone demethylase belonging to the PHF2/8 subfamily of the JmjC demethylases. It mainly localizes in the nucleus and contributes to transcriptional activation by removing mono-and di-methyl groups from lysine residues 9 and 27 of Histone H3. Kdm7a is involved in multiple biological processes, such as embryonic, neural, and skeletal development, and is associated with various diseases including cancer, inflammation, osteoporosis, and osteoarthritis [2].

In mice, conditional deletion of the Kdm7a gene specifically in osterix-expressing osteoprogenitor cells led to an increase in cancellous bone mass, with more osteoblasts and bone formation, and fewer osteoclasts, marrow adipocytes, and bone resorption. Kdm7a deficiency also prevented ovariectomy-induced bone loss, suggesting its role in bone homeostasis [4]. In another study, in vivo knockdown of Kdm7a in the dentate gyrus neuron of mice hippocampus via AAV-based stereotaxic microinjection decreased the expression of c-Fos, a marker of neuron activity, and led to impairment of emotion and memory [3]. In human chondrocytes, individual silencing of Kdm7a demonstrated its role in mediating the protective effects on H3K79 methylation and osteoarthritis [1].

In conclusion, Kdm7a plays crucial roles in multiple biological processes. Studies using gene-knockout or knockdown mouse models have revealed its significance in bone homeostasis, neuron functions, and osteoarthritis. These findings contribute to understanding the mechanisms of related diseases and may provide potential therapeutic targets for diseases like osteoporosis and osteoarthritis.