Endocrine Unit, University of California, San Francisco and Veterans Affairs Health Care System, San Francisco, California, USA.
Bioengineering & Biomaterials Micro-CT and Imaging Facility, University of California, San Francisco, San Francisco, California, USA.
Endocrinology. 2020 Dec 1;161(12). doi: 10.1210/endocr/bqaa179.
Ephrin B2 is critical for endochondral bone development. In this study, we investigated its role in fracture repair by deleting ephrin B2 in type II collagen (Col.2) expressing cells. We used a nonstable tibia fracture model to evaluate fracture repair at 3 sites: intramembranous bone formation, endochondral bone formation, and intramedullary bone formation. We observed that during fracture repair, deletion of ephrin B2 impaired periosteal stem cell activation, inhibited their proliferation, decreased their survival, and blocked their differentiation into osteoblasts and chondrocytes. In addition, deletion of ephrin B2 decreased vascular endothelial growth factor production as well as vascular invasion into the fracture site. These changes led to reduced cartilage to bone conversion in the callus with decreased new bone formation, resulting in impaired fracture repair. Our data indicate that ephrin B2 in Col2-expressing cells is a critical regulator of fracture repair, pointing to a new and potentially targetable mechanism to enhance fracture repair.
Ephrin B2 对于软骨内骨发育至关重要。在这项研究中，我们通过删除 Col.2 表达细胞中的 Ephrin B2 来研究其在骨折修复中的作用。我们使用非稳定胫骨骨折模型在 3 个部位评估骨折修复：膜内骨形成、软骨内骨形成和骨髓内骨形成。我们观察到，在骨折修复过程中，Ephrin B2 的缺失会损害骨膜干细胞的激活，抑制其增殖，降低其存活率，并阻止其分化为成骨细胞和软骨细胞。此外，Ephrin B2 的缺失会减少血管内皮生长因子的产生以及血管向骨折部位的侵入。这些变化导致骨痂中软骨向骨的转化减少，新骨形成减少，从而导致骨折修复受损。我们的数据表明，Col2 表达细胞中的 Ephrin B2 是骨折修复的关键调节因子，这为增强骨折修复提供了一个新的、潜在的可靶向机制。
