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

Abstract

Summary Background Osteoarthritis (OA) of the distal intertarsal (DIT) and tarsometatarsal (TMT) joints occurs commonly. Synovial fluid (SF) biomarkers of collagen and bone turnover have potential clinical value. Objectives To measure SF biomarker concentrations from DIT and TMT joints in adult horses and determine if they correlate with radiographic OA severity and are higher in joints with radiographic OA compared to controls. Study design Cross‐sectional. Methods Radiographic OA of DIT and TMT joints was evaluated from adult horses (5–35 years old). Overall radiographic scores divided horses into those with mild or moderate radiographic OA (16 joints from 9 horses) or controls (13 joints from 9 horses). Direct biomarkers of OA (Carboxypropeptide of type II collagen = CPII, carboxy‐neoepitope of type II collagen exposed after collagenase‐cleavage = C2C, Bone alkaline phosphatase = BAP and Chondroitin sulfate epitope = CS846) were measured via ELISA and CPII/C2C was calculated. Biomarkers were correlated with radiographic findings and concentrations from those with radiographic OA to control joints and were compared. Results Concentrations of CPII (R = 0.84, P<0.001), C2C (R = 0.69, P<0.001) and BAP (R = 0.41, P = 0.03) as well as CPII/C2C (R = 0.69, P<0.001) values positively correlated with overall radiographic scores. Adjusted means ± s.d., after controlling for age, for CPII (P<0.001), C2C (P<0.001), CPII/C2C (P = 0.004) and BAP (P = 0.05) were significantly higher in DIT and TMT joints with radiographic OA (CPII: 2174.45 ± 1064.01; C2C: 233.52 ± 51.187; CPII/C2C: 9.01 ± 4.09; BAP: 21.98 ± 15.34) compared to controls (CPII: 594.53 ± 463.05; C2C: 153.12 ± 48.95; CPII/C2C: 3.96 ± 2.38; BAP: 12.76 ± 3.61). CPII (P<0.001), C2C (P = 0.001) and CPII/C2C (P = 0.001) were significantly higher with moderate radiographic OA (CPII: 2444.61 ± 772.78; C2C: 248.90 ± 44.94; CPII/C2C: 9.47 ± 2.97) compared to controls (CPII: 658.38 ± 417.36; C2C: 156.49 ± 47.61; CPII/C2C: 4.15 ± 2.04), with CPII also showing significantly higher concentrations (P = 0.04) with mild radiographic OA compared (1515.00 ± 584.95) to controls (658.38 ± 417.36). There were no differences in CS846 concentrations between radiographic OA and control joints. Age positively correlated with CPII (R = 0.48, P = 0.01) and C2C (R = 0.44, P = 0.02) concentrations. Main limitations Radiographic OA was assessed, not clinical lameness. Controls were not age‐matched to those with spontaneous radiographic OA. Conclusions There is an association between collagen (CPII, C2C and CPII/C2C) and bone (BAP) biomarkers and radiographic OA in the distal tarsal joints of horses.

Treating Full Depth Cartilage Defects with Intraosseous Infiltration of Plasma Rich in Growth Factors: An Experimental Study in Rabbits

“…In our study, C2C and HA biomarker levels were assessed in rabbits with acute cartilage full depth defect 28, 56, and 84 days after IA infiltration of PRGF together with IO infiltration of saline solution or PRGF (CT and TRT group, respectively). The utility of C2C concentration, both in serum and SF, to monitor disease progression and response to treatment has been reported in various animal models, including dogs, 39-41 sheep, 42 horses, 43 mice, 44 guinea pigs, 45 and rabbits. 46,47 In all studies, a correlation between C2C levels and OA severity was observed, and its serum or SF concentration was higher after joint damage.…”

Intra-osseous infiltration of adipose mesenchymal stromal cells and plasma rich in growth factors to treat acute full depth cartilage defects in a rabbit model: Serum osteoarthritis biomarkers and macroscopical assessment

“…It has been proven that C2C is increased in initial stages of OA, while it is decreased in chronic stages ( 35 , 36 ). The utility of C2C concentration to monitor disease progression and response to treatment has been reported in several animal models, including dogs ( 37 , 38 ), sheep ( 39 ), horses ( 40 ), mice ( 41 ), and guinea pigs ( 42 ). Another well-studied OA biomarker is hyaluronic acid (HA).…”

Soluble and EV-Associated Diagnostic and Prognostic Biomarkers in Knee Osteoarthritis Pathology and Detection

“…To investigate if SF biomarker concentrations corresponded with the severity of radiographic OA and were higher in joints with radiographic OA compared to controls, Coppelman et al examined SF biomarker concentrations from distal intertarsal and tarsometatarsal joints in adult horses. They confirmed that overall radiographic scores have a positive correlation with the C2C value concentration in equine SF [ 127 ]. In addition to the correlations identified with several other injury-related biomarkers, the higher levels of C2C in SF following injury show that an acute knee injury is linked to the rapid and long-lasting local breakdown of type II collagen [ 128 ].…”