To B (Bone Morphogenic Protein-2) or Not to B (Bone Morphogenic Protein-2): Mesenchymal Stem Cells May Explain the Protein's Role in Osteosarcomagenesis.

Chunfeng Xu,Wei Sun,Mingjie Wang,Lingfei Wei,Yuelian Liu,Behrouz Zandieh-Doulabi

doi:10.3389/fcell.2021.740783

Abstract

Osteosarcoma (OS), a primary malignant bone tumor, stems from bone marrow-derived mesenchymal stem cells (BMSCs) and/or committed osteoblast precursors. Distant metastases, in particular pulmonary and skeletal metastases, are common in patients with OS. Moreover, extensive resection of the primary tumor and bone metastases usually leads to bone defects in these patients. Bone morphogenic protein-2 (BMP-2) has been widely applied in bone regeneration with the rationale that BMP-2 promotes osteoblastic differentiation of BMSCs. Thus, BMP-2 might be useful after OS resection to repair bone defects. However, the potential tumorigenicity of BMP-2 remains a concern that has impeded the administration of BMP-2 in patients with OS and in populations susceptible to OS with severe bone deficiency (e.g., in patients with genetic mutation diseases and aberrant activities of bone metabolism). In fact, some studies have drawn the opposite conclusion about the effect of BMP-2 on OS progression. Given the roles of BMSCs in the origination of OS and osteogenesis, we hypothesized that the responses of BMSCs to BMP-2 in the tumor milieu may be responsible for OS development. This review focuses on the relationship among BMSCs, BMP-2, and OS cells; a better understanding of this relationship may elucidate the accurate mechanisms of actions of BMP-2 in osteosarcomagenesis and thereby pave the way for clinically safer and broader administration of BMP-2 in the future. For example, a low dosage of and a slow-release delivery strategy for BMP-2 are potential topics for exploration to treat OS.

Highlights

Osteosarcoma (OS), a primary bone neoplasm, is rare, with an incidence of only one to three confirmed cases per 1 million people in the world each year, it comprises ∼20% of newly diagnosed bone tumors (Dorfman and Czerniak, 1995; Klein and Siegal, 2006; Mirabello et al, 2009b)
Researchers should pay attention to the differences between various OS cell lines and the diverse OS subtypes. These differences are responsible for the contradictory roles of bone morphogenic protein-2 (BMP-2) in OS development
All authors contributed to the article and approved the submitted version

Summary

INTRODUCTION

Osteosarcoma (OS), a primary bone neoplasm, is rare, with an incidence of only one to three confirmed cases per 1 million people in the world each year, it comprises ∼20% of newly diagnosed bone tumors (Dorfman and Czerniak, 1995; Klein and Siegal, 2006; Mirabello et al, 2009b). Mesenchymal stem cells (MSCs) are identified as the origin of OS and are capable of differentiating into osteoblasts, a process that can be accelerated by BMP-2. BMP-2 is involved in the progression of OS, suggesting that complicated crosstalk may exist among OS, BMP-2, and MSCs. As multipotent mesenchymal stromal cells, MSCs are universally found in almost all connective tissues (Horwitz et al, 2005; da Silva Meirelles et al, 2006). Gauthaman et al (2012) found that umbilical cord-derived MSCs from Wharton’s jelly suppressed the proliferation and migration of MG-63 cells (a human OS cell line) in vitro; in a Kaposi sarcoma model, MSCs inhibited tumor progression (Khakoo et al, 2006).

LIMITATIONS

SUMMARY