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Lysyl Oxidase Production by Murine C3H10T1/2 Mesenchymal Stem Cells Is Increased by TGFßs and Differentially Modulated by Mechanical Stimuli.
Pancheri, Nicholas M; Ellingson, Allison J; Marchus, Colin R; Durgesh, Vibhav; Verhage, Tabitha; Yensen, Nicholas; Schiele, Nathan R.
Afiliación
  • Pancheri NM; Department of Chemical & Biological Engineering, University of Idaho, Moscow, Idaho, USA.
  • Ellingson AJ; Department of Chemical & Biological Engineering, University of Idaho, Moscow, Idaho, USA.
  • Marchus CR; Department of Chemical & Biological Engineering, University of Idaho, Moscow, Idaho, USA.
  • Durgesh V; Department of Mechanical Engineering, University of Idaho, Moscow, Idaho, USA.
  • Verhage T; Department of Chemical & Biological Engineering, University of Idaho, Moscow, Idaho, USA.
  • Yensen N; Department of Chemical & Biological Engineering, University of Idaho, Moscow, Idaho, USA.
  • Schiele NR; Department of Chemical & Biological Engineering, University of Idaho, Moscow, Idaho, USA.
Stem Cells Dev ; 33(13-14): 355-364, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38770821
ABSTRACT
Tendons are frequently injured and have limited regenerative capacity. This motivates tissue engineering efforts aimed at restoring tendon function through strategies to direct functional tendon formation. Generation of a crosslinked collagen matrix is paramount to forming mechanically functional tendon. However, it is unknown how lysyl oxidase (LOX), the primary mediator of enzymatic collagen crosslinking, is regulated by stem cells. This study investigates how multiple factors previously identified to promote tendon formation and healing (transforming growth factor [TGF]ß1 and TGFß2, mechanical stimuli, and hypoxia-inducible factor [HIF]-1α) regulate LOX production in the murine C3H10T1/2 mesenchymal stem cell (MSC) line. We hypothesized that TGFß signaling promotes LOX activity in C3H10T1/2 MSCs, which is regulated by both mechanical stimuli and HIF-1α activation. TGFß1 and TGFß2 increased LOX levels as a function of concentration and time. Inhibiting the TGFß type I receptor (TGFßRI) decreased TGFß2-induced LOX production by C3H10T1/2 MSCs. Low (5 mPa) and high (150 mPa) magnitudes of fluid shear stress were applied to test impacts of mechanical stimuli, but without TGFß2, loading alone did not alter LOX levels. Low loading (5 mPa) with TGFß2 increased LOX at 7 days greater than TGFß2 treatment alone. Neither HIF-1α knockdown (siRNA) nor activation (CoCl2) affected LOX levels. Ultimately, results suggest that TGFß2 and appropriate loading magnitudes contribute to LOX production by C3H10T1/2 MSCs. Potential application of these findings includes treatment with TGFß2 and appropriate mechanical stimuli to modulate LOX production by stem cells to ultimately control collagen matrix stiffening and support functional tendon formation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta1 / Factor de Crecimiento Transformador beta2 / Células Madre Mesenquimatosas / Proteína-Lisina 6-Oxidasa Límite: Animals Idioma: En Revista: Stem Cells Dev Asunto de la revista: HEMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta1 / Factor de Crecimiento Transformador beta2 / Células Madre Mesenquimatosas / Proteína-Lisina 6-Oxidasa Límite: Animals Idioma: En Revista: Stem Cells Dev Asunto de la revista: HEMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos