In:
Nature Communications, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2018-08-24)
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-2 n /Smurf1 e ) 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-2 d /Smurf1 n ). We screen a chalcone derivative, i.e., 2-(4-cinnamoylphenoxy)acetic acid, which effectively inhibits Smurf1 activity and increases BMP signaling. For BMP-2 n /Smurf1 e 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-2 n /Smurf1 e mice. This study demonstrates a precision medicine-based bone anabolic strategy for age-related osteoporosis.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-018-05974-z
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2018
detail.hit.zdb_id:
2553671-0
