Loading-Induced Bone Formation is Mediated by Wnt1 Induction in Osteoblast-Lineage Cells

Abstract

Mechanical loading on the skeleton stimulates bone formation. Although the exact mechanism underlying this process remains unknown, a growing body of evidence indicates that the Wnt signaling pathway is necessary for the skeletal response to loading. Recently, we showed that Wnts produced by osteoblast lineage cells mediate the osteo-anabolic response to tibial loading in adult mice. Here, we report that Wnt1 specifically plays a crucial role in mediating the mechano-adaptive response to loading. Independent of loading, short-term loss of Wnt1 in the Osx-lineage resulted in decreased cortical bone area in the tibias of 5-month old mice. In females, strain-matched loading enhanced periosteal bone formation in Wnt1F/F controls, but not in Wnt1F/F; OsxCreERT2 knockouts. In males, strain-matched loading increased periosteal bone formation in both control and knockout mice; however, the periosteal relative bone formation rate was 65% lower in Wnt1 knockouts versus controls. Together, these findings show that Wnt1 supports adult bone homeostasis and mediates the bone anabolic response to mechanical loading.

Effect of nicotinamide mononucleotide on osteogenesis in MC3T3-E1 cells against inflammation-induced by lipopolysaccharide

“…A previous study reported that a reduction in β-catenin expression within chondrocytes resulted in the degeneration of articular cartilage typically seen in osteoarthritis [31]. Furthermore, Wnt1 has been identified as a regulator of both homeostasis and anabolic processes in the bone tissue of adult mice, particularly during bone formation induced by mechanical loading [32].…”