Relationship between synovial fluid levels of glycosaminoglycans, hydroxyproline and general MMP activity and the presence and severity of articular cartilage change on the proximal articular surface of P1

Abstract

Summary Reasons for performing study: Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting horses and leads to degeneration of articular cartilage. Diagnosis is based on clinical signs in combination with radiography, which is relatively insensitive and provides only an indication of accumulated damage. Alternative methods, such as molecular markers, are therefore needed that can quantitatively, reliably and sensitively detect osteoarthritic changes in the joints at an early stage of the disease. If such markers are to be used reliably, it is important to know the relationship between marker concentration and cartilage composition. Objectives: To study the relationship between cartilage composition, synovial fluid levels of glycosaminoglycans (GAGs), hydroxyproline (Hyp) and general matrix metalloproteinase (MMP) activity, and the presence and severity of articular cartilage damage on the articular surface of P1. Methods: Synovial fluid (SF) was collected from the metacarpophalangeal joints of 60 mature horses, and levels of GAGs, Hyp and general MMP activity were determined. Further, GAG and denatured collagen content of the articular cartilage were determined at the dorsal articular margin of P1 (site 1) and central cavity (site 2). The presence and severity of cartilage change was quantified using the cartilage degeneration index (CDI), measured at the same 2 sites. Correlations between SF parameters, cartilage composition and degree of cartilage degeneration were sought using correlation analysis. Results: There was no correlation between GAG or Hyp content of SF and the amount of GAGs or denatured collagen, respectively, in cartilage. In joints with moderate to severe cartilage damage, the GAG content of site 1 was significantly lower than in joints with no to minimal cartilage change (P = 0.005) and there was a negative correlation between the amount of denatured collagen and GAG content at site 1 in all joints (r =−0.39, P = 0.002). Further, in joints with moderate to severe cartilage damage, there was a significant positive correlation between MMP activity in SF and Hyp levels in SF (r = 0.72, P<0.001) and CDI at sites 1 (r = 0.46, P=0.03) and 2 (r = 0.43, P = 0.04). Conclusions: General MMP activity in joints with moderate to severe cartilage damage is related to the severity of those cartilage changes and to Hyp levels in SF. Glycosaminoglycan levels in SF are not directly related to MMP activity, GAG content of articular cartilage or severity of cartilage change. Potential relevance: Glycosaminoglycan levels in SF are not helpful for the early detection of cartilage lesions. In damaged joints, Hyp levels may give an indication of the severity of cartilage change as they are strongly related to MMP activity, but do not qualify as markers for the presence or absence of cartilage lesions.

Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self‐limiting inflammation when evaluated in an lipopolysaccharide induced synovitis model

“…The synovial fluid supernatant was divided and stored at ‐80°C for future evaluation. From these aliquots in the CB‐MSC feasibility study and the LPS/CB‐MSCs co‐administration study, glycosaminoglycan release was determined using the dimethylmethylene blue assay. Prostaglandin E 2 (PGE 2 ) , C‐propeptide of type II collagen (CP‐II) , type II collagen cleavage neopeptide (C2C) , and chondroitin sulfate CS‐846 epitope of aggrecan synthesis were evaluated using commercially available ELISA kits (CP‐II, C2C, CS‐846; PGE 2 ).…”

A systematic review and meta‐analysis of the efficacy of platelet‐rich plasma products for treatment of equine joint disease

“…6 In clinical practice, PRP products are considered valuable treatment options for equine joint disease but a widely communicated agreement on its clinical efficacy is lacking. 15,61 This systematic review evaluated the efficacy of PRP prod-…”

“…66,67 As previously discussed, there are inconsistent results in in vitro studies on this issue. 46,47 While leukocytes concentrations are best kept low due to their release of pro-inflammatory cytokines such as IL-1, TNF, IL-6, MMP-8 and MMP-9, 61,68 an elevation in the levels of GFs of PRP products are linked to the presence of leukocytes. 45,69 While both, P-PRP and L-PRP demonstrate a favourable impact on OA, 50,56 further research is necessary to evaluate the impact of white blood cells on treatment efficacy and the potential for increased joint damage relating to their intra-articular persistence.…”

Alterations to the synovial invaginations of the navicular bone are associated with pathology of both the navicular apparatus and distal interphalangeal joint when evaluated using high field MRI

“…It has been established that the balance of synovial mediators such as certain matrix metalloproteinases and prostaglandins/leukotrienes changes in osteoarthritic joints. 17 , 18 , 19 , 20 , 21 Additionally, increased stress when the DIPJ is placed under extensive axial rotation and collateromotion, 22 especially in horses with greater medial/lateral imbalance, 23 , 24 may then lead to the formation of new synovial invaginations.…”