Attenuated Wnt/β-catenin signalling mediates methotrexate chemotherapy-induced bone loss and marrow adiposity in rats

►Cancer chemotherapy often causes bone loss, marrow adiposity and haematopoietic defects, yet the underlying mechanisms remain unclear. ►This study investigated roles of Wnt/β-catenin signalling in changes to bone marrow cell differentiation in rats after antimetabolite methotrexate chemotherapy. ►Changes in bone marrow adipogenic, osteogenic, haematopoietic and osteoclastogenic differentiation potential after MTX chemotherapy are associated with attenuated Wnt/β-catenin signalling. ►Concurrent administration of BIO, a GSK-3β inhibitor that activates Wnt/β-catenin signalling, partially abrogates MTX-induced changes in the bone marrow. ►These findings suggest a potentially important role of Wnt/β-catenin signalling in MTX chemotherapy-induced cellular changes to the bone marrow microenvironment.