Related Experiment Video
Updated: May 13, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Dynamic profiling of BMSC-dECM reveals accumulation of core matrisome proteins suppresses osteogenic differentiation
Mei Li1, Weilai Zhu2, Mingyu Hu2
1Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, the First Affiliated Hospital of Ningbo University, Ningbo University, Ningbo, Zhejiang, People's Republic of China.
Introduction:
The extracellular matrix (ECM) of bone mesenchymal stem cells (BMSCs) plays a critical role in tissue development and regeneration. Rather than being inert, the ECM exhibits a dynamic structure that determines cell fate.
Objectives:
The aim of this study is to investigate the dynamic composition, functional properties, and underlying mechanisms of BMSC-ECM during osteogenic differentiation. We propose that dynamic alterations in BMSC-ECM, particularly in critical matrix proteins, are essential to regulate osteogenic differentiation and bone regeneration.
Methods:
Dynamic ECM from BMSCs was collected at different time points during culture with or without osteogenic induction, followed by decellularization. A mouse tibial defect model was introduced to assess bone regeneration in vivo. Proteomics was used to analyze the dynamic protein composition pattern, while a comparative transcriptomic analysis further determined the impact of dynamic BMSC-dECM on cellular mRNA profile.
Results:
Decellularized ECMs (dECMs) from late noninduced BMSCs exhibited distinct functional properties compared to the other groups. While early noninduced, early osteogenic (Os)-induced and late Os-induced dECMs promoted bone regeneration, late noninduced dECM dramatically inhibited this process. The protein composition of dECMs, rather than the structure or total ECM content, was the key factor determining their dynamic function. Accumulation of core matrisome during noninduced culture resulted in the inhibition of its function. Consistently, the gene expression profiles of replanted BMSCs on early noninduced/Os-induced dECM and late Os-induced dECM were similar, leaving the late noninduced dECM separate. Moreover, the core matrisome of the external dECM negatively regulated intracellular gene expression. Versican (VCAN) and Asporin (ASPN) might be the key ECM proteins influencing bone regeneration.
Conclusions:
Accumulation of the core matrisome during noninduction led to solidification and the inactivation of bone regeneration. Targeting the core matrisome might effectively avoid the drawbacks of noninduced dECM, providing novel strategies for developing highly bioactive stem cell-derived dECM.
