Mapk7, a member of the Mitogen-activated protein kinases (MAPKs) family, controls cell differentiation, proliferation, and survival [2]. It is involved in multiple signaling pathways such as MEF2C/PTEN/AKT, Lrp6/β -catenin, and is associated with various biological processes like bone development, cell inflammation, and adipogenesis [1,2]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In cartilage-specific Mapk7-deleted (Col2a1-cre; Mapk7f/f) mice, vertebral defects including kyphosis and osteopenia occurred. Mapk7 loss decreased MEF2C expression, activated PTEN, and opposed PI3K/AKT signaling in vertebral growth plate chondrocytes, impairing chondrocyte hypertrophy and vertebral ossification. Systemic activation of AKT in vivo rescued these defects [1]. In mesenchymal stem cells (MSCs), depletion of Mapk7 by crossing Prx1-Cre mice to Mapk7flox/flox led to severe low bone mass, fat accumulation in bone marrow, and osteoporosis in mice. Mapk7 promoted osteogenic differentiation and inhibited adipogenic differentiation of MSCs by activating Wnt/β-catenin signaling through phosphorylating Lrp6 at Ser1490 [2]. In zebrafish, morpholino-induced mapk7 knockdown led to body curvature and delayed vertebral ossification, and in human mesenchymal stem cells (hMSCs), MAPK7 silencing impaired osteogenesis [3].

In conclusion, Mapk7 plays a crucial role in bone-related biological processes, such as vertebral development and osteogenesis-adipogenesis balance in MSCs. The KO/CKO mouse models and other loss-of-function experiments in zebrafish and hMSCs have significantly contributed to understanding its functions in these processes, which may provide insights for treating spine developmental disorders and osteoporosis [1,2,3].