| 1. |
- Kurenkova, A. D., et al.
(författare)
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Notch Signaling Regulates the Chondrogenic Potential of Both Articular Chondrocytes and Their Progenitors During Expansion
- 2023
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Ingår i: Stem Cells. - 1066-5099. ; 41:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Trompet, Dana, 1993, et al.
(författare)
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Stimulation of skeletal stem cells in the growth plate promotes linear bone growth
- 2024
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Ingår i: JCI INSIGHT. - 2379-3708. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Recently, skeletal stem cells were shown to be present in the epiphyseal growth plate (epiphyseal skeletal stem cells, epSSCs), but their function in connection with linear bone growth remains unknown. Here, we explore the possibility that modulating the number of epSSCs can correct differences in leg length. First, we examined regulation of the number and activity of epSSCs by Hedgehog (Hh) signaling. Both systemic activation of Hh pathway with Smoothened agonist (SAG) and genetic activation of Hh pathway by Patched1 (Ptch1) ablation in Pthrp-creER Ptch1(fl/fl )tdTomato mice promoted proliferation of epSSCs and clonal enlargement. Transient intra-articular administration of SAG also elevated the number of epSSCs. When SAG-containing beads were implanted into the femoral secondary ossification center of 1 leg of rats, this leg was significantly longer 1 month later than the contralateral leg implanted with vehicle-containing beads, an effect that was even more pronounced 2 and 6 months after implantation. We conclude that Hh signaling This opens therapeutic possibilities for the treatment of differences in leg length.
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