Fibrous tissue of subchondral cystic lesions in horses produce local mediators and neutral metalloproteinases and cause bone resorption in vitro

Objectives-To define the release of nitric oxide (NO), prostaglandin E2 (PG E?,), and the neutral metalloproteinases (NMPs) in horses with subchondral cystic lesions (SCL) and to study bone resorption triggered by conditioned media of fibrous tissue of SCL in vitro. Study Design-Equine explant cultures of fibrous tissue of SCL, and synovial membrane and articular cartilage of normal horses and horses affected with moderate and severe osteoarthritis were performed. NO, PGE2, and NMP conce ntrations of media samples were measured, and osteoclast formation and acti vation was studied in vitro. Animals-Experiment 1: 32 horses with SCL (n = 8), normal joints (7), and jo ints with moderate (7) and severe (10) osteoarthritis (OA). Experiment 2: 2 2 horses with SCL (n = 3), normal joints (7), and chip fractures (12). Expe riment 3: Conditioned media of fibrous tissue from 3 horses with SCL of the medial femoral condyle (n = 1), distal metacarpal bone (1), and tarsal bon e (1). Methods-Determinations of local mediator concentrations were made with the Griess assay for NO and an enzyme immunoassay kit for PGE2 concentrations i n biological fluids. Enzyme activities were assessed with radiolabeled subs trates indicating collagenolytic, gelatinolytic, and caseinolytic activitie s. The resorption pit assay was used to assess osteoclast recruitment and a ctivity. Results-Fibrous tissue of SCL produced NO, PGE2, and NMPs. Of all the varia bles measured, PGE2 concentrations were the highest in cystic tissue of SCL compared with synovial membrane and articular cartilage from normal joints and joints with chip fractures, indicating that this mediator may play an important role in pathological bone resorption associated with SCL. These f indings were supported by the observation that conditioned media of SCL tis sue were capable of recruiting osteoclasts and increasing their activity. Conclusion-Fibrous tissue of SCL released NO, PGE2, and NMPs into the cultu re media. It is suspected that intralesional fibrous tissue may play an act ive role in the pathological process of bone resorption occurring in SCL in horses and may be partly responsible for the maintenance, slow healing rat e, and expansion of these lesions. Clinical Relevance-Understanding the pathogenesis of SCL will help to estab lish successful therapy in horses affected with SCL. (C) Copyright 2000 by The American College of Veterinary Surgeons.