Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014, Donostia-San Sebastian, Spain.
POLYMAT, University of the Basque Country (UPV-EHU), 20018, Donostia-San Sebastian, Spain.
Stem Cell Res Ther. 2024 Apr 29;15(1):124. doi: 10.1186/s13287-024-03735-y.
Recombinant human bone morphogenetic protein 2 (rhBMP-2) and human bone marrow mesenchymal stromal cells (hBM-MSCs) have been thoroughly studied for research and translational bone regeneration purposes. rhBMP-2 induces bone formation in vivo, and hBM-MSCs are its target, bone-forming cells. In this article, we studied how rhBMP-2 drives the multilineage differentiation of hBM-MSCs both in vivo and in vitro.
rhBMP-2 and hBM-MSCs were tested in an in vivo subcutaneous implantation model to assess their ability to form mature bone and undergo multilineage differentiation. Then, the hBM-MSCs were treated in vitro with rhBMP-2 for short-term or long-term cell-culture periods, alone or in combination with osteogenic, adipogenic or chondrogenic media, aiming to determine the role of rhBMP-2 in these differentiation processes.
The data indicate that hBM-MSCs respond to rhBMP-2 in the short term but fail to differentiate in long-term culture conditions; these cells overexpress the rhBMP-2 target genes DKK1, HEY-1 and SOST osteogenesis inhibitors. However, in combination with other differentiation signals, rhBMP-2 acts as a potentiator of multilineage differentiation, not only of osteogenesis but also of adipogenesis and chondrogenesis, both in vitro and in vivo.
Altogether, our data indicate that rhBMP-2 alone is unable to induce in vitro osteogenic terminal differentiation of hBM-MSCs, but synergizes with other signals to potentiate multiple differentiation phenotypes. Therefore, rhBMP-2 triggers on hBM-MSCs different specific phenotype differentiation depending on the signalling environment.
重组人骨形态发生蛋白 2（rhBMP-2）和人骨髓间充质基质细胞（hBM-MSCs）已被广泛研究用于研究和转化骨再生目的。rhBMP-2 在体内诱导骨形成，而 hBM-MSCs 是其靶细胞，成骨细胞。在本文中，我们研究了 rhBMP-2 如何在体内和体外驱动 hBM-MSCs 的多能分化。
rhBMP-2 和 hBM-MSCs 在体内皮下植入模型中进行测试，以评估它们形成成熟骨和进行多能分化的能力。然后，hBM-MSCs 用 rhBMP-2 进行短期或长期细胞培养处理，单独或与成骨、成脂或软骨形成培养基联合使用，旨在确定 rhBMP-2 在这些分化过程中的作用。
数据表明，hBM-MSCs 在短期内对 rhBMP-2 有反应，但在长期培养条件下无法分化；这些细胞过度表达 rhBMP-2 的靶基因 DKK1、HEY-1 和 SOST 成骨抑制剂。然而，与其他分化信号结合，rhBMP-2 作为多能分化的增强剂发挥作用，不仅促进成骨分化，而且促进体外和体内的成脂分化和软骨分化。
总之，我们的数据表明，rhBMP-2 单独不能诱导 hBM-MSCs 的体外成骨终末分化，但与其他信号协同作用增强多种分化表型。因此，rhBMP-2 根据信号环境触发 hBM-MSCs 不同的特定表型分化。
