RESUMO
The Runt-related transcription factor (Runx) family plays various roles in the homeostasis of cartilage. Here, we examined the role of Runx2 and Runx3 for osteoarthritis development in vivo and in vitro. Runx3-knockout mice exhibited accelerated osteoarthritis following surgical induction, accompanied by decreased expression of lubricin and aggrecan. Meanwhile, Runx2 conditional knockout mice showed biphasic phenotypes: heterozygous knockout inhibited osteoarthritis and decreased matrix metallopeptidase 13 (Mmp13) expression, while homozygous knockout of Runx2 accelerated osteoarthritis and reduced type II collagen (Col2a1) expression. Comprehensive transcriptional analyses revealed lubricin and aggrecan as transcriptional target genes of Runx3, and indicated that Runx2 sustained Col2a1 expression through an intron 6 enhancer when Sox9 was decreased. Intra-articular administration of Runx3 adenovirus ameliorated development of surgically induced osteoarthritis. Runx3 protects adult articular cartilage through extracellular matrix protein production under normal conditions, while Runx2 exerts both catabolic and anabolic effects under the inflammatory condition.
Assuntos
Anabolizantes , Cartilagem Articular , Osteoartrite , Animais , Camundongos , Agrecanas/genética , Agrecanas/metabolismo , Anabolizantes/farmacologia , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Camundongos Knockout , Osteoartrite/genética , Osteoartrite/metabolismoRESUMO
Purpose: We aimed to develop a rat flexor tendon repair model that could be applied to experiments in similar clinical settings. Methods: We prepared 3 different combinations of sutures in rat flexor tendons: group A had 3 single peripheral sutures plus a 2-strand core suture; group B had 3 figure-of-eight peripheral sutures alone; and group C had 3 figure-of-eight peripheral sutures plus a 2-strand core suture. We examined the in vitro tensile strength of the repaired tendons by a biomechanical test, the rerupture rate within 3 weeks, and histological findings in vivo. Results: Group C displayed the greatest ultimate strength by the mechanical test. The flexor tendons in group C did not rerupture within 3 weeks after surgery, whereas many of those in groups A and B reruptured. Fibrous scar tissue was observed in the gap of the tendon stumps in groups A and B, but not in group C. Conclusions: The combination of figure-of-eight peripheral sutures and a 2-strand core suture provided the repaired rat flexor tendon with enough strength to prevent rerupture without cast fixation or immobilization after surgery. Clinical relevance: This combination of sutures is useful to reproduce flexor tendon repair similar to that performed in clinical settings and will contribute to various translational experiments in vivo.