Articular cartilage has a limited capacity for self-repair and clinical approaches to cartilage regeneration are needed. The only such approach developed to date involves an expansion of primary autologous chondrocytes in culture, followed by their reimplantation into a cartilage defect. However, because of the formation of fibrocartilage instead of hyaline cartilage, the outcome is often not satisfactory. It happens due to the de-differentiation of chondrocytes during the expansion step. Indeed, articular chondrocytes are non-proliferative and require partial or complete dedifferentiation before actively proliferating. In recent years stem/progenitor cells in articular cartilage (artSPCs) have been described. These cells maintain their own population and renew articular cartilage in sexually mature mice. artSPCs can, theoretically, be superior to chondrocytes, for repairing damaged cartilage. Accordingly, here, we searched for conditions that allow rapid expansion of both artSPCs and chondrocytes with simultaneous preservation of their ability to form hyaline cartilage. Among the modulators of Wnt, Notch, and FGF signaling and of cell adhesion screened, only fibronectin and modulators of the Notch pathway promoted the rapid expansion of artSPCs. Surprisingly, both inhibition and activation of the pathway had this effect. However, only inhibition of Notch during expansion facilitated the chondrogenic potential of both artSPCs and primary chondrocytes, whereas activation of this pathway abrogated this potential entirely. This effect was the same for murine and human cells. Our present observations indicate that Notch signaling is the major regulator of the chondrogenic capacity of both artSPCs and chondrocytes during their expansion.

中文翻译：

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Notch 信号在扩张过程中调节关节软骨细胞及其祖细胞的软骨形成潜能。

关节软骨的自我修复能力有限，需要软骨再生的临床方法。迄今为止开发的唯一此类方法涉及在培养物中扩增原代自体软骨细胞，然后将它们重新植入软骨缺损处。然而，由于形成的是纤维软骨而不是透明软骨，因此结果往往不尽如人意。它的发生是由于软骨细胞在扩张步骤中的去分化。事实上，关节软骨细胞是非增殖性的，在活跃增殖之前需要部分或完全去分化。近年来，已经描述了关节软骨中的干/祖细胞 (artSPC)。这些细胞维持它们自己的种群并更新性成熟小鼠的关节软骨。理论上，artSPC 可以 优于软骨细胞，用于修复受损的软骨。因此，在这里，我们搜索了允许 artSPC 和软骨细胞快速扩增并同时保留其形成透明软骨的能力的条件。在筛选的 Wnt、Notch 和 FGF 信号转导以及细胞粘附的调节剂中，只有纤连蛋白和 Notch 通路的调节剂促进了 artSPC 的快速扩增。令人惊讶的是，该通路的抑制和激活都有这种效果。然而，只有在扩张过程中抑制 Notch 才能促进 artSPC 和原代软骨细胞的软骨形成潜能，而激活该途径则完全消除了这种潜能。这种效果对于小鼠和人类细胞是相同的。