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

• DOI: 10.1038/s41467-020-17417-9
• Publication Date: 2020-08-27T10:04:31Z
• Authors: Min Jiang; Ruiwu Liu; Lixian Liu; Alexander Kot; Xueping Liu; Wenwu Xiao; Junjing Jia; Yuanpei Li; Kit S. Lam; Wei Yao
• Keywords: Bone remodeling

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