1 TMJ Biology and Regenerative Medicine Laboratory, College of Dental Medicine, Columbia University Medical Center, New York, NY, USA.
2 Department of OB/GYN, Division of Reproductive Sciences, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
J Dent Res. 2018 Mar;97(3):329-337. doi: 10.1177/0022034517735094. Epub 2017 Oct 11.
Angiogenesis is a complex, multicellular process that is critical for bone development and generation. Endochondral ossification depends on an avascular cartilage template that completely remodels into vascularized bone and involves a dynamic interplay among chondrocytes, osteoblasts, and endothelial cells. We have discovered fibrocartilage stem cells (FCSCs) derived from the temporomandibular joint (TMJ) mandibular condyle that generates cartilage anlagen, which is subsequently remodeled into vascularized bone using an ectopic transplantation model. Here we explore FCSC and endothelial cell interactions during vascularized bone formation. We found that a single FCSC colony formed transient cartilage and host endothelial cells may participate in bone angiogenesis upon subcutaneous transplantation in a nude mouse. FCSCs produced an abundance of the proangiogenic growth factor vascular endothelial growth factor A and promoted the proliferation of human umbilical vein endothelial cells (HUVECs). Using a fibrinogen gel bead angiogenesis assay experiment, FCSC cell feeder layer induced HUVECs to form significantly shorter and less sprouts than D551 fibroblast controls, suggesting that FCSCs may initially inhibit angiogenesis to allow for avascular cartilage formation. Conversely, direct FCSC-HUVEC contact significantly enhanced the osteogenic differentiation of FCSCs. To corroborate this idea, upon transplantation of FCSCs into a bone defect microenvironment, FCSCs engrafted and regenerated intramembranous bone. Taken together, we demonstrate that the interactions between FCSCs and endothelial cells are essential for FCSC-derived vascularized bone formation. A comprehensive understanding of the environmental cues that regulate FCSC fate decisions may contribute to deciphering the mechanisms underlying the role of FCSCs in regulating bone formation.
血管生成是一个复杂的、多细胞的过程，对骨骼的发育和生成至关重要。软骨内骨化依赖于一个无血管的软骨模板，该模板完全重塑为血管化的骨骼，并涉及软骨细胞、成骨细胞和内皮细胞之间的动态相互作用。我们已经发现源自颞下颌关节（TMJ）下颌髁的纤维软骨干细胞（FCSC），它产生软骨原基，随后使用异位移植模型重塑为血管化骨骼。在这里，我们探讨了血管化骨形成过程中 FCSC 和内皮细胞的相互作用。我们发现，一个单独的 FCSC 菌落形成短暂的软骨，并且在裸鼠皮下移植时，宿主内皮细胞可能参与骨血管生成。FCSC 产生大量促血管生成生长因子血管内皮生长因子 A，并促进人脐静脉内皮细胞（HUVEC）的增殖。使用纤维蛋白原凝胶珠血管生成测定实验，FCSC 细胞饲养层诱导 HUVEC 形成的血管比 D551 成纤维细胞对照更短且更少分支，这表明 FCSC 可能最初抑制血管生成以允许无血管软骨形成。相反，FCSC 与 HUVEC 的直接接触显著增强了 FCSC 的成骨分化。为了证实这一观点，将 FCSC 移植到骨缺损微环境中后，FCSC 植入并再生膜内骨。总之，我们证明了 FCSC 和内皮细胞之间的相互作用对于 FCSC 衍生的血管化骨形成是必不可少的。全面了解调节 FCSC 命运决定的环境线索可能有助于解析 FCSC 调节骨形成作用的机制。
