Osteochondritis dissecans (OCD) in Horses – Molecular Background of its Pathogenesis and Perspectives for Progenitor Stem Cell Therapy

Abstract

Osteochondrosis (osteochondrosis dissecans; OCD) is a disease syndrome of growing cartilage related to different clinical entities such as epiphysitis, subchondral cysts and angular carpal deformities, which occurs in growing animals of all species, including horses. Nowadays, these disorders are affecting increasing numbers of young horses worldwide. As a complex multifactorial disease, OCD is initiated when failure in cartilage canals because of existing ischemia, chondrocyte biogenesis impairment as well as biochemical and genetic disruptions occur. Recently, particular attention have been accorded to the definition of possible relations between OCD and some metabolic disorders; in this way, implication of mitochondrial dysfunctions, endoplasmic reticulum disruptions, oxidative stress or endocrinological affections are among the most considered axes for future researches. As one of the most frequent cause of impaired orthopaedic potential, which may result in a sharp decrease in athletic performances of the affected animals, and lead to the occurrence of complications such as joint fragility and laminitis, OCD remains as one of the primary causes of considerable economic losses in all sections of the equine industry. It would therefore be important to provide more information on the exact pathophysiological mechanism(s) underlying early OC(D) lesions, in order to implement innovative strategies involving the use of progenitor stem cells, which are considered nowadays as a promising approach to regenerative medicine, with the potential to treat numerous orthopaedic disorders, including osteo-degenerative diseases, for prevention and reduction of incidence of the disease, not only in horses, but also in human medicine, as the equine model is already widely accepted by the scientific community and approved by the FDA, for the research and application of cellular therapies in the treatment of human conditions.

Proteome Alterations in Equine Osteochondrotic Chondrocytes

“…Indeed, the progression of cartilage lesions and the presence of intra-articular fragments can also develop in early onset osteoarthritis (OA) [4,5]. The molecular events that can drive the chondrocyte biogenesis impairment and extracellular matrix (ECM) alteration, common features in OC, seem to be related to mitochondrial and endoplasmic reticulum alterations, oxidative stress, and endocrinological dysfunction [8].…”

Vitamin K and equine osteocalcin: an enigma explored

“…Pre-sale x-rays are now a requirement for all Thoroughbred sales. However, lesions visible on x-ray are always of pathological concern (Bourebaba et al 2019).…”

“…It is evident that measures to reduce the incidence of DOD lesions occurring are necessary. In order to do this, an increased understanding of the underlying mechanism involved in the pathogenesis of these diseases is imperative (Desjardin et al 2014;Bourebaba et al 2019).…”

“…Osteochondrosis is an important DOD in young horses (Desjardin et al 2014). The primary lesion is caused by a defect in the growing cartilage during endochondral ossification (Bourebaba et al 2019). It may lead to the development of osteochondritis dissecans (OCD) in which the primary lesion separates from the underlying bone.…”

“…In humans' closure of the growth plates occurs at the onset of adolescence (puberty) which can vary between individuals (Kronenberg 2003). Most bones in the body develop via this process of endochondral ossification as depicted in Figure 2.10 (Mackie et al 2008;Bourebaba et al 2019). It is therefore the primary mechanism that determines an animal's underlying skeletal morphology, and can be influenced by several factors, in particular physiological conditions and nutritional status (Lepeule et al 2013).…”