Growth Plate Pathology in the Mucopolysaccharidosis Type VI Rat Model—An Experimental and Computational Approach

Abstract

Background: Mucopolysaccharidoses (MPS) are a group of inherited metabolic diseases caused by impaired function or absence of lysosomal enzymes involved in degradation of glycosaminoglycans. Clinically, MPS are skeletal dysplasias, characterized by cartilage abnormalities and disturbances in the process of endochondral ossification. Histologic abnormalities of growth cartilage have been reported at advanced stages of the disease, but information regarding growth plate pathology progression either in humans or in animal models, as well as its pathophysiology, is limited. Methods: Histological analyses of distal femur growth plates of wild type (WT) and mucopolysaccharidosis type VI (MPS VI) rats at different stages of development were performed, including quantitative data. Experimental findings were then analyzed in a theoretical scenario. Results: Histological evaluation showed a progressive loss of histological architecture within the growth plate. Furthermore, in silico simulation suggest the abnormal cell distribution in the tissue may lead to alterations in biochemical gradients, which may be one of the factors contributing to the growth plate abnormalities observed, highlighting aspects that must be the focus of future experimental works. Conclusion: The results presented shed some light on the progression of growth plate alterations observed in MPS VI and evidence the potentiality of combined theoretical and experimental approaches to better understand pathological scenarios, which is a necessary step to improve the search for novel therapeutic approaches.

Treatment of skeletal and non-skeletal alterations of Mucopolysaccharidosis type IVA by AAV-mediated gene therapy

“…Moreover, the rat provides a unique possibility to study arthritis induced by oil adjuvants, since adjuvants alone do not induce models of rheumatoid arthritis in other animal species, such as the mouse 30 . In addition, for MPSVI disease, the MPSVI rat model develops a more severe bone phenotype than the MPSVI mouse model 26,[50][51][52] , in agreement with our MPSIVA rat model. All these studies highlight the translational impact of the rat models in skeletal-related diseases.…”

Effects of Maternal Diabetes on Prenatal Development of The Vertebral Column in The Albino Rat and Possible Protective Role of Arachidonic Acid

“…The hypertrophied chondrocytes in the calcification zone degenerate, leaving lacunae that are invaded by cells from the marrow-filled centrum gaps. These results support the previous findings of Guevara-Morales et al (2020) who clarified that the epiphyseal growth plate is made up of chondrocytes at various stages of development. Round in shape, resting zone chondrocytes serve as the stem-like cells that restock the proliferative chondrocyte pool.…”

Maternal alloxan exposure induces damage in rat offspring lumbar vertebrae and protective role of arachidonic acid

“…In the calcification zone, the hypertrophied chondrocytes were degenerated leaving lacunae, which were invaded by cells from the marrow filled spaces of the centrum. These results supported the previous findings of earlier studies that clarified the structure of the epiphyseal growth plate containing one cell type, the chondrocyte, at different stages of differentiation [33,34]. Resting zone chondrocytes display a round morphology, and act as the stem-like cells that replenish the pool of proliferative chondrocytes.…”