MY‐1‐Loaded Nano‐Hydroxyapatite Accelerated Bone Regeneration by Increasing Type III Collagen Deposition in Early‐Stage ECM via a Hsp47‐Dependent Mechanism

The extracellular matrix (ECM) plays a crucial part in regulating stem cell function through its distinctive mechanical and chemical effect. Therefore, it is worth studying how to activate the driving force of osteoblast cells by dynamic changing of ECM and accelerate the bone regeneration. In this research, a novel peptide MY‐1 is designed and synthesized. To achieve its sustained releasing, the nano‐hydroxyapatite (nHA) is chosen as the carrier of MY‐1 by mixed adsorption. The results reveal that the sustainable releasing of MY‐1 regulates the synthesis and secretion of ECM from rat bone marrow mesenchymal stem cells (rBMSCs), which promotes the cell migration and osteogenic differentiation in the early stage of bone regeneration. Further analyses demonstrate that MY‐1 increases the expression and nuclear translocation of β‐catenin, and then upregulates the level of heat shock protein 47 (Hsp47), thereby accelerating the synthesis and secretion of type III collagen (Col III) at the early stage. Finally, the promoted rapid transformation of Col III to Col I at late stage benefits the bone regeneration. Hence, this study can provide a theoretical basis for the local application of MY‐1 in bone regeneration. The peptide MY‐1‐loaded nHA can extend the MY‐1 releasing period in the local bone defect. Then, MY‐1 is endocytosed by parathyroid hormone 1 receptor (PTH1R) and induces the upregulation and nuclear translocation of β‐catenin, thereby promoting the expression of Hsp47 and accelerating the synthesis and secretion of collagen at early stage, thus promoting the early osteogenesis and bone regeneration.