Work

NLK knockdown in hBMSCs enhance repair of critical-size bone defects by modulating neurogenic and osteogenic differentiation

Year: 2025

Type: article

Abstract: Nemo-like kinase (NLK), an evolutionarily conserved MAP kinase-related kinase, is highly expressed in neural tissues and critically regulates cell proliferation, migration, and apoptosis by regulating numerous transcriptional molecules. Despite the widespread application of mesenchymal stem cells (MSCs) in regenerative medicine, the functional role and molecular mechanisms of NLK in MSC-mediated tissue repair remained poorly understood. Here, the dual regulatory effects of NLK on both neurogenic and osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) were investigated. The results showed that NLK acted as a potent inhibitor of hBMSC neurogenesis in vitro and suppressed osteogenesis both in vitro and in vivo. Mechanistically, NLK downregulated the transcriptional coactivators LEF1 and TCF4, thereby impairing their pro-differentiation functions during neural and bone formation. These findings suggested that NLK-mediated suppression of LEF1/TCF4 signaling might hinder endogenous bone repair by dual inhibition of hBMSC neurogenic and osteogenic capacities. Targeting this pathway could offer novel therapeutic strategies for enhancing bone defect regeneration and inform the design of advanced biomaterials for bone tissue engineering.

Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DOI: 10.1016/j.bbadis.2025.167870

Authors: Ke LI, Mengdi LI, Zhongning LIU, Jingwen YANG, Jian LI, Ting JIANG

Institutions: Peking University, Peking University School and Hospital of Stomatology

Language: English

Topic: Mesenchymal stem cell research

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,010