Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.
Dev Dyn. 2020 Jun;249(6):711-722. doi: 10.1002/dvdy.158. Epub 2020 Feb 10.
Cruciate ligament (CL) and patellar tendon (PT) are important elements of the knee joint, uniting femur, patella, and tibia into a single functional unit. So far, knowledge on the developmental mechanism of CL, PT, and patella falls far behind other skeletal tissues.
Here, employing various lineage tracing strategies we investigate the cellular sources and dynamics that drive CL, PT, and patella formation during mouse embryonic development. We show that Gdf5 and Gli1 are generally expressed in the same cell population that only contributes to CL, but not PT or patella development. In addition, Col2 is expressed in two independent cell populations before and after joint cavitation, where the former contributes to the CL and the dorsal part of the PT and the latter contributes to the patella. Moreover, Prrx1 is always expressed in CL and PT progenitors, but not patella progenitors where it is switched off after joint cavitation. Finally, we reveal that patella development employs different cellular dynamics before and after joint cavitation.
Our findings delineate the expression changes of several skeletogenesis-related genes before and after joint cavitation, and provide an indication on the cellular dynamics underlying ligament, tendon, and sesamoid bone formation during embryogenesis.
十字韧带(CL)和髌腱(PT)是膝关节的重要组成部分,将股骨、髌骨和胫骨连接成一个单一的功能单元。到目前为止,CL、PT 和髌骨的发育机制的知识远远落后于其他骨骼组织。
在这里,我们采用了各种谱系追踪策略,研究了在小鼠胚胎发育过程中驱动 CL、PT 和髌骨形成的细胞来源和动力学。我们表明,Gdf5 和 Gli1 通常在仅对 CL 但不对 PT 或髌骨发育有贡献的同一细胞群中表达。此外,Col2 在关节腔形成前后的两个独立细胞群中表达,前者有助于 CL 和 PT 的背侧部分,后者有助于髌骨的形成。此外,Prrx1 始终在 CL 和 PT 祖细胞中表达,但不在关节腔形成后表达,此时它在髌骨祖细胞中关闭。最后,我们揭示了髌骨发育在关节腔形成前后采用不同的细胞动力学。
我们的研究结果描绘了关节腔形成前后几个与骨骼发生相关的基因的表达变化,并为胚胎发生过程中韧带、肌腱和籽骨形成的细胞动力学提供了指示。