Anabolic actions of Notch on mature bone

Abstract

Notch controls skeletogenesis, but its role in the remodeling of adult bone remains conflicting. In mature mice, the skeleton can become osteopenic or osteosclerotic depending on the time point at which Notch is activated or inactivated. Using adult EGFP reporter mice, we find that Notch expression is localized to osteocytes embedded within bone matrix. Conditional activation of Notch signaling in osteocytes triggers profound bone formation, mainly due to increased mineralization, which rescues both age-associated and ovariectomy-induced bone loss and promotes bone healing following osteotomy. In parallel, mice rendered haploinsufficient in γ-secretase presenilin-1 (Psen1), which inhibits downstream Notch activation, display almost-absent terminal osteoblast differentiation. Consistent with this finding, pharmacologic or genetic disruption of Notch or its ligand Jagged1 inhibits mineralization. We suggest that stimulation of Notch signaling in osteocytes initiates a profound, therapeutically relevant, anabolic response.

Dibenzazepine-Loaded Nanoparticles Induce Local Browning of White Adipose Tissue to Counteract Obesity

“…Notch signaling plays fundamental roles in regulating cell-cell communication and cell-fate determination during multiple tissue and organ development. For example, it has been reported to influence muscle regeneration, 22,23 bone formation, 24,25 and angiogenesis. 26,27 Nevertheless, the role of Notch in adipogenesis and adipocyte plasticity has just begun to be understood.…”

Blood flow controls bone vascular function and osteogenesis

“…Notch signalling also has important cell-autonomous roles in the osteoblast lineage and preserves mesenchymal progenitors by preventing excessive differentiation of these cells6970. Notch activation in mature osteocytes triggers a strong skeletal anabolic response in adult mice, which is sufficient to rescue age-associated and ovariectomy-induced bone loss71. As osteocyte processes physically interact with the vascular endothelium72, it would be worthwhile to investigate whether different cell types communicate through direct Notch-ligand interactions.…”

Blocking FSH induces thermogenic adipose tissue and reduces body fat

“…Tissues were subject to hematoxylin/eosin staining or immunocytochemistry by protocols described earlier 55 . Images were captured using the Keyence or Zeiss microscope.…”