Inhibition of osteoblastic Smurf1 promotes bone formation in mouse models of distinctive age-related osteoporosis

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

2 Scopus Citations
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Author(s)

  • Chao Liang
  • Songlin Peng
  • Jie Li
  • Jun Lu
  • Daogang Guan
  • Feng Jiang
  • Cheng Lu
  • Fangfei Li
  • Xiaojuan He
  • Hailong Zhu
  • Dazhi Yang
  • Bao-Ting Zhang
  • Aiping Lu
  • Ge Zhang

Detail(s)

Original languageEnglish
Article number3428
Journal / PublicationNature Communications
Volume9
Publication statusPublished - 24 Aug 2018

Link(s)

Abstract

Bone morphogenetic protein (BMP) signaling is essential for osteogenesis. However, recombinant human BMPs (rhBMPs) exhibit large inter-individual variations in local bone formation during clinical spinal fusion. Smurf1 ubiquitinates BMP downstream molecules for degradation. Here, we classify age-related osteoporosis based on distinct intraosseous BMP-2 levels and Smurf1 activity. One major subgroup with a normal BMP-2 level and elevated Smurf1 activity (BMP-2n/Smurf1e) shows poor response to rhBMP-2 during spinal fusion, when compared to another major subgroup with a decreased BMP-2 level and normal Smurf1 activity (BMP-2d/Smurf1n). We screen a chalcone derivative, i.e., 2-(4-cinnamoylphenoxy)acetic acid, which effectively inhibits Smurf1 activity and increases BMP signaling. For BMP-2n/Smurf1e mice, the chalcone derivative enhances local bone formation during spinal fusion. After conjugating to an osteoblast-targeting and penetrating oligopeptide (DSS)6, the chalcone derivative promotes systemic bone formation in BMP-2n/Smurf1e mice. This study demonstrates a precision medicine-based bone anabolic strategy for age-related osteoporosis.

Research Area(s)

  • Targeted bone remodelling, Drug screening, Osteoporosis

Citation Format(s)

Inhibition of osteoblastic Smurf1 promotes bone formation in mouse models of distinctive age-related osteoporosis. / Liang, Chao; Peng, Songlin; Li, Jie; Lu, Jun; Guan, Daogang; Jiang, Feng; Lu, Cheng; Li, Fangfei; He, Xiaojuan; Zhu, Hailong; Au, D. W.T.; Yang, Dazhi; Zhang, Bao-Ting; Lu, Aiping; Zhang, Ge.

In: Nature Communications, Vol. 9, 3428, 24.08.2018.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

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