Lee S, Remark L H, Josephson A M, Leclerc K, Lopez E Muiños, Kirby D J, Mehta Devan, Litwa H P, Wong M Z, Shin S Y, Leucht P
Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, USA.
Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany.
NPJ Regen Med. 2021 May 28;6(1):29. doi: 10.1038/s41536-021-00139-x.
Adult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation OPC proliferation is controlled by Notch signaling, while differentiation is initiated by activation of canonical Wnt signaling. The temporospatial separation of Notch and Wnt signal activation during the early stages of bone regeneration suggests crosstalk between the two pathways. In vitro and in vivo manipulation of the two essential pathways demonstrate that Wnt activation leads to initiation of osteogenic differentiation and at the same time inhibits Notch signaling, which results in termination of the proliferative phase. Here, we establish canonical Wnt signaling as a key regulator that facilitates the crosstalk between OPC proliferation and differentiation during intramembranous, primary bone healing.
成骨祖细胞（OPC）的精确作用调控着成人骨再生。然而，OPC增殖与分化相联系并因此受到调控的机制尚未明确。在此，我们提供证据表明，在膜内骨形成过程中，OPC增殖受Notch信号控制，而分化则由经典Wnt信号的激活启动。骨再生早期Notch和Wnt信号激活的时空分离提示这两条信号通路之间存在相互作用。对这两条关键信号通路进行体外和体内操作表明，Wnt激活可导致成骨分化的启动，同时抑制Notch信号，从而导致增殖期的终止。在此，我们确立经典Wnt信号作为关键调节因子，其在膜内原发性骨愈合过程中促进OPC增殖与分化之间的相互作用。
