Abstract

Osteochondritis dissecans (OCD) in equids, especially in sport horses, has become a growing issue as it contributes to the occurrence of lameness. Thus the aim of this study was to investigate the cytophysiological properties of OCD chondrocytes including expression of chondrogenic genes, apoptosis, mitochondria dynamics and autophagy. Horse chondrocytes were isolated from healthy (HE) and OCD cartilages. Properties of cells were evaluated using multiple assays e.g., polymerase chain reaction (PCR), immunofluorescence, Western blot. OCD chondrocytes were characterized by increased apoptosis and senescence. Expression of chondrogenic genes (vimentin, aggrecan) was decreased while mRNA levels of matrix metalloproteinase 13 significantly upregulated in comparison to HE cells. Moreover, OCD cells displayed increased mitochondrial fusion while fission events were diminished. Interestingly, chaperone mediated autophagy was triggered in those cells and it predominated over macroautophagy. Furthermore, co-culture of LPS-treated chondrocytes with adipose-derived stem cells (ASC) decreased p62/sequestosome 1 (SQSTM) and increases MMP-13 expression in OCD cells. Our results suggest that OCD affected horse chondrocytes are characterized by senescent phenotype due to endoplasmic reticulum stress and mitochondria dynamics deterioration. Expression of chondrogenic markers is decreased in those cells while expression of chaperone mediated autophagy (CMA)-related genes increased. Increased malfunctioning of cells leads to loss of their functionality and capacity to maintain tissue homeostasis.

Highlights

  • Osteochondrosis (OC) is a disease of the cartilage which negatively affects joint homeostasis

  • In our study we revealed that osteochondritis dissecans (OCD) chondrocytes share a set of common characteristics to previously studied OA tissue

  • In our study we have revealed that mitochondria from OCD chondrocytes are characterized by increased fusion which allows for the exchange of content including DNA, and metabolites between neighboring organelles, including damaged or senescent ones, in consequence promoting their survival [58]

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Summary

Introduction

Osteochondrosis (OC) is a disease of the cartilage which negatively affects joint homeostasis. OC is found in humans and in other mammals like dogs and horses. It is considered a serious condition which contributes to reduced mobility, poor performance and early retirement of sport horses causing adversefinancial consequences. Thickened cartilage in its basal layers is characterized by deterioration of cellular differentiation which leads to necrosis, retention and development of fissures. Severe joint inflammation may lead to the development of osteoarthritis [1]. 50% of OCD-affected horses suffer from bilateral lesions, one of the lesions is more severe. Due to the high costs of surgical intervention and poor prognosis in the treatment of large lesions, the economic consequences of OCD are extensive [2]

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