Anabolic actions of Notch on mature bone

Peng Liu, Yilin Ping, Meng Ma, Demao Zhang, Connie Liu, Samir Zaidi, Song Gao, Yaoting Ji, Feng Lou, Fanyuan Yu, Ping Lu, Agnes Stachnik, Mingru Bai, Chengguo Wei, Liaoran Zhang, Ke Wang, Rong Chen, Maria I. New, David W. Rowe, Tony YuenLi Sun, Mone Zaidi

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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 ovariectomyinduced 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 almostabsent 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.

Original languageEnglish
Pages (from-to)E2152-E2161
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number15
StatePublished - 12 Apr 2016


  • Aging
  • Osteoporosis
  • Skeletal mineralization
  • Therapeutic target


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