Identification of osteogenic progenitor cell-targeted peptides that augment bone formation

Min Jiang, Ruiwu Liu, Lixian Liu, Alexander Kot, Xueping Liu, Wenwu Xiao, Junjing Jia, Yuanpei Li, Kit S. Lam and Wei Yao ()
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Min Jiang: The University of California at Davis Medical Center
Ruiwu Liu: The University of California at Davis Medical Center
Lixian Liu: The University of California at Davis Medical Center
Alexander Kot: The University of California at Davis Medical Center
Xueping Liu: The University of California at Davis Medical Center
Wenwu Xiao: The University of California at Davis Medical Center
Junjing Jia: The University of California at Davis Medical Center
Yuanpei Li: The University of California at Davis Medical Center
Kit S. Lam: The University of California at Davis Medical Center
Wei Yao: The University of California at Davis Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Activation and migration of endogenous mesenchymal stromal cells (MSCs) are critical for bone regeneration. Here, we report a combinational peptide screening strategy for rapid discovery of ligands that not only bind strongly to osteogenic progenitor cells (OPCs) but also stimulate osteogenic cell Akt signaling in those OPCs. Two lead compounds are discovered, YLL3 and YLL8, both of which increase osteoprogenitor osteogenic differentiation in vitro. When given to normal or osteopenic mice, the compounds increase mineral apposition rate, bone formation, bone mass, and bone strength, as well as expedite fracture repair through stimulated endogenous osteogenesis. When covalently conjugated to alendronate, YLLs acquire an additional function resulting in a “tri-functional” compound that: (i) binds to OPCs, (ii) targets bone, and (iii) induces “pro-survival” signal. These bone-targeted, osteogenic peptides are well suited for current tissue-specific therapeutic paradigms to augment the endogenous osteogenic cells for bone regeneration and the treatment of bone loss.

Date: 2020
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DOI: 10.1038/s41467-020-17417-9

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