Molecular monitoring of equine joint homeostasis

Abstract

Diseases affecting synovial joints are a major cause of chronic disability both in humans and in companion animal species, most notably dogs and horses. As progressive deterioration of the articular cartilage is the hallmark of degenerative joint disease or osteoarthritis, research efforts traditionally tended to focus primarily on cartilage pathology. However, in recent years it has become clear that synovial joints should be considered intricate organs in their own right, with each of the constituent tissues (cartilage, bone, and synovial membrane) interacting with each other both in health and disease. Moreover, with the advent of modern molecular biology techniques, the importance of synovial inflammation in disease development and progression has become increasingly recognized. These realizations have spurred the need for tools that allow a more comprehensive, integral study of synovial joint homeostasis. This review provides a brief overview of synovial joint biology and the concept of joint homeostasis, followed by a discussion of methods that may be used to study joint homeostasis (varying from in vitro tissue culture to in vivo imaging) including specific advantages and limitations of each approach. It then zooms in on one such approach, synovial fluid biomarker analysis, as a promising avenue in synovial joint research, highlighting some results from equine studies performed in the author's own laboratory that illustrate how such studies may help shed light on in vivo joint homeostasis and therapeutic modulation thereof. The review concludes with some future perspectives and promising developments in the field.

Evaluation of the anti-inflammatory effects of two platelet-rich gel supernatants in an in vitro system of cartilage inflammation

“…In general, OA is characterized by a catabolic state of the articular cartilage, in which pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-a) and interleukin 1 (IL-1), are up-regulated and they, in turn, induce gene up-regulation and local tissue production of cartilage-associated degradation enzymes as matrix metalloproteinases (MMPs) and nitric oxide synthases (NOSs) and pro-inflammatory substances as prostaglandins, leukotrienes and nitric oxide, which finally produce joint damage and pain [2,4,5].…”

The association between collagen and bone biomarkers and radiographic osteoarthritis in the distal tarsal joints of horses

“…This is unlikely to have any major contribution on our results since circulating epitopes are further digested in the systemic circulation . Due to the dynamic composition of SF and its direct proximity to the articular cartilage , it is likely that each sampled joint was the source of higher concentrations. It is also important to note that radiographic changes in the tarsus have variable correlation with clinical lameness .…”

“…CPII and C2C are protein epitopes that can be measured in synovial fluid to evaluate recent type II collagen synthesis (CPII) or degradation (C2C) . Measuring concentrations of biomarkers in synovial fluid provides a real‐time assessment of disease activity within a particular joint due to its dynamic composition and direct proximity to the articular cartilage . When there is an increase in either synthesis or degradation of type II collagen in an adult animal, it is in response to change in tissue integrity and/or metabolism of the joint from aetiologies such as: osteoarthritis, traumatic injury, substantial change in exercise, inflammation, etc.…”

“…When there is an increase in either synthesis or degradation of type II collagen in an adult animal, it is in response to change in tissue integrity and/or metabolism of the joint from aetiologies such as: osteoarthritis, traumatic injury, substantial change in exercise, inflammation, etc. . Such responses have been evaluated using biomarkers in multiple equine studies examining horses with spontaneous disease, experimentally created disease, and in response to exercise .…”

Development of diagnostic models for canine osteoarthritis based on serum and joint fluid mid‐infrared spectral data using five different discrimination and classification methods

“…Compared with the serum data, the separation for the joint fluid samples are less clear. The specific reason is not well understood, but there is evidence that the metabolic processes within synovial fluid are distinct from those in the systemic circulation, and the differences in the relative concentrations of key molecular components may be expected to contribute to the spectral information …”