Expression of Musashi-1 Increases in Bone Healing.

Miguel Padial-Molina,Pedro Hernandez-Cortes,Clara Candido-Corral,Pablo Galindo-Moreno,Vicente Crespo-Lora,Dario Abril-Garcia,Nati Martin-Morales,Francisco O’Valle

doi:10.3390/ijms22073395

Miguel Padial-Molina, Pedro Hernandez-Cortes + Show 6 more

Open Access

https://doi.org/10.3390/ijms22073395

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Abstract

Musashi-1 (MSI1) is an RNA-binding protein that regulates progenitor cells in adult and developing organisms to maintain self-renewal capacities. The role of musashi-1 in the bone healing environment and its relation with other osteogenic factors is unknown. In the current study, we analyze the expression of MSI1 in an experimental model of rat femoral bone fractures. We also analyze the relation between MSI1 expression and the expression of two osteogenic markers: periostin (POSTN) and runt-related transcription factor 2 (RUNX2). We use histological, immunohistochemical, and qPCR techniques to evaluate bone healing and the expression of MSI1, POSTN, and RUNX2 over time (4, 7, and 14 days). We compare our findings with non-fractured controls. We find that in bone calluses, the number of cells expressing MSI1 and RUNX2 increase over time and the intensity of POSTN expression decreases over time. Within bone calluses, we find the presence of MSI1 expression in mesenchymal stromal cells, osteoblasts, and osteocytes but not in hypertrophic chondrocytes. After 14 days, the expression of MSI1, POSTN, and RUNX2 was significantly correlated. Thus, we conclude that musashi-1 potentially serves in the osteogenic differentiation of mesenchymal stromal cells and bone healing. Therefore, further studies are needed to determine the possibility of musashi-1′s role as a clinical biomarker of bone healing and therapeutic agent for bone regeneration.

Highlights

Bone tissue has self-repair properties depending on mesenchymal stromal cells’(MSCs’) recruitment and differentiation, angiogenesis, formation of a bone fracture callus, and endochondral and intramembranous bone ossification
We evaluate the number and distribution of MSI1 positive cells in different tissue compartments of the bone calluses after inducing femoral diaphysis fractures without osteosynthesis
We analyze the relation between MSI1, RUNX2, and POSTN-positive cells within different tissue compartments and their overall mRNA

Summary

Introduction

Bone tissue has self-repair properties depending on mesenchymal stromal cells’. (MSCs’) recruitment and differentiation, angiogenesis, formation of a bone fracture callus, and endochondral and intramembranous bone ossification. MSCs can be found in the bone marrow, endosteum, and periosteum. During bone repair, these are the main sources of cells for the healing process [1]. That is the reason why MSCs have been proposed for the treatment of several bone diseases. The Musashi family is a group of two RNA-binding proteins with two ribonucleoprotein-type RNA-binding domains (RBDs) [2].

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