Articular cartilage degeneration and bone adaptation due to lack of dystrophin in mice

Author(s)

dos Santos, Jose Fontes ^[1] ; Lazzarin, Mariana Cruz ^[1] ; de Araujo Baptista, Vivianne Izabelle ^[1] ; Quintana, Hananiah Tardivo ^[1] ; Ribeiro, Daniel Araki ^[1] ; de Oliveira, Flavia ^[1]

Affiliation

^[1] Univ Fed Sao Paulo UNIFESP, Dept Biociencias, Rua Silva Jardim, 136 Lab 328, BR-11015020 Santos, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF BONE AND MINERAL METABOLISM; v. 40, n. 1 SEP 2021.
• Web of Science Citations: 0

Abstract

Introduction Duchenne muscular dystrophy is caused by the absence of dystrophin. This study aimed to investigate femoral morphological characteristics of lack of dystrophin in MDX mice, considering that this model, different from DMD patient, is not influenced by corticosteroids administration and limited ambulation. Materials and methods Proximal femur of male 16-week-old Control and MDX mice were submitted to histological, morphometric (volume density of articular cartilage, compact bone, trabecular bone and bone marrow; articular cartilage layers area; articular cartilage cell area), and immunohistochemistry analysis for RUNX-2, RANK-L, MMP-2, MMP-9, Caspase-3 and KI-67. Results MDX showed loss of linearity of articular cartilage with subchondral bone transition and elevation of this subchondral bone to the articular surface when compared with control. In addition, MDX presented morphological difference in the pantographic network of collagen fibers. Volume density of trabecular bone tissue was higher in the MDX than Control, but volume density of articular cartilage was lower in MDX (p < 0.05). The articular cartilage layers and chondrocytes area were significantly smaller in MDX than Control. These results associated to MMPs and osteogenic markers of proximal femur revealed an adaptation process as a consequence of lack of dystrophin. Conclusions The morphological changes observed in the bone tissue of the MDX may be not only secondary to muscle weakness or chronic use of corticosteroids but also our results indicate connections between decrease of cartilage thickness, collagen network alteration and consequent subchondral changes that may lead to articular cartilage degeneration and bone adaptation mechanism in MDX mice. (AU)

• FAPESP's process: 14/22211-6 - Regeneration process characteristics of skeletal muscle of different embryological origins in mdx mice submitted to aerobic exercise
• Grantee: Mariana Cruz Lazzarin
• Support Opportunities: Scholarships in Brazil - Master