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

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.

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Acknowledgements

Authors would like to thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for the scholarship (grant number 14/22211-6).

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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by JFdS, MCL, VIdAB and HTQ. Supervision was made by FdO and DAR. The first draft of the manuscript was written by JFdS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Flavia de Oliveira.

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dos Santos, J.F., Lazzarin, M.C., Baptista, V.I.A. et al. Articular cartilage degeneration and bone adaptation due to lack of dystrophin in mice. J Bone Miner Metab (2021). https://doi.org/10.1007/s00774-021-01270-x

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Keywords

  • MDX mice
  • Duchenne muscular dystrophy
  • Articular cartilage
  • Bone
  • Collagen