Involvement of mitochondrial dysfunction and ER-stress in the physiopathology of equine osteochondritis dissecans (OCD).

The research article comprises investigations about the role of mitochondrial dysfunction and ER-stress in the development of osteochondritis dissecans (OCD), a common bone disorder in horses. The study reveals insights into the cause of OCD and the factors that may increase predisposition to the disease.

Introduction and Study Objectives

• The article focuses on Osteochondrosis (OC), a defective bone development condition affecting various mammalian species including horses. Within horses, this condition is significant as it triggers joint swelling, stiffness, and lameness, impacting about 30% of the population.
• OCD, an outcome of OC, is a controversial topic as its physiology is not fully understood and the genes involved in genetic predisposition have not been determined.
• The purpose of the study is to compare healthy and OC-affected samples, and identify the role of mitochondrial activity and ER-stress in the disorder’s development.

Methodology of Study

• The study involved a comparative shot-gun proteomic analysis of samples taken from two healthy and two OC-affected 18-month-old French Trotters.
• 83 and 53 modulated proteins were identified from healthy and OC-affected samples respectively, revealing that these proteins impact various biological pathways.
• Transmission electron microscopy unveiled standard features of mitochondrial swelling and ER-stress, such as empty, large mitochondria, and hyper-dilated rough endoplasmic reticulum in both OC lesions and predisposed cartilage.

Results of Study

• The findings reveal abnormal fibril organization surrounding chondrocytes and abnormal features at the ossification front.
• The combination of these findings with results from quantitative trait loci and whole genome sequencing identified approximately 140 functional candidate genes carrying potential damaging mutations in 30 QTL regions.

Conclusion

• OCD lesions may result from defective hypertrophic terminal differentiation, leading to impaired cartilage and bone biomechanical properties, making them prone to fractures.
• The study’s findings offer new insights into the molecular physiopathology and genetic basis of OCD, identifying 11 modulated proteins and several candidate mutations.