Kdm7a, also known as Lysine-specific demethylase 7A, KIAA1718 or JHDM1D, is an α-ketoglutarate-and Fe(II)-dependent demethylase belonging to the PHF2/8 subfamily of the JmjC demethylases. It is mainly localized in the nucleus and functions to remove mono-and di-methyl groups from the lysine residues 9 and 27 of Histone H3, contributing to transcriptional activation. It is involved in multiple biological processes such as embryonic, neural, and skeletal development, and is associated with various diseases including cancer, inflammation, and osteoporosis [1].

In mice, conditional deletion of the Kdm7a gene specifically in osterix-expressing osteoprogenitor cells led to a significant increase in cancellous bone mass, with more osteoblasts and bone formation, and fewer osteoclasts, marrow adipocytes and bone resorption. The mutant mice's bone marrow stromal cells showed enhanced osteogenic and suppressed adipogenic differentiation, and osteoclastic precursor cells had impaired osteoclast differentiation. Mechanistically, Kdm7a upregulates the expression of fibroblast activation protein α (FAP) and receptor activator of nuclear factor κB ligand (RANKL) in bone marrow stromal cells [3]. In another study, in vivo knockdown of Kdm7a in dentate gyrus neuron of mice hippocampus via Adeno-associated virus-based stereotaxic microinjection led to decreased expression of c-Fos, a marker of neuron activity, and impairment of emotion and memory in behavior assays, suggesting Kdm7a affects neuron functions by regulating immediate early genes [2].

In conclusion, Kdm7a is crucial for normal development and is involved in multiple biological processes. Studies using mouse models, like gene knockout or knockdown, have revealed its role in bone homeostasis, where it balances osteoblast and osteoclast differentiation, and in neuron functions, affecting emotion and memory. These findings may provide potential therapeutic targets for osteoporosis and neurological disorders.

References:

1. Li, Chang-Yun, Liu, Yan-Jun, Tao, Fan, Yang, Guan-Jun, Chen, Jiong. 2023. Lysine-specific demethylase 7A (KDM7A): A potential target for disease therapy. In Biochemical pharmacology, 216, 115799. doi:10.1016/j.bcp.2023.115799. https://pubmed.ncbi.nlm.nih.gov/37696455/

2. Wang, Yifan, Hong, Qin, Xia, Yueyue, Zhang, Zhao, Wen, Bo. 2023. The Lysine Demethylase KDM7A Regulates Immediate Early Genes in Neurons. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2301367. doi:10.1002/advs.202301367. https://pubmed.ncbi.nlm.nih.gov/37565374/

3. Shan, Liying, Yang, Xiaoli, Liao, Xiaoxia, Li, Xiaoxia, Wang, Baoli. 2024. Histone demethylase KDM7A regulates bone homeostasis through balancing osteoblast and osteoclast differentiation. In Cell death & disease, 15, 136. doi:10.1038/s41419-024-06521-z. https://pubmed.ncbi.nlm.nih.gov/38346941/