A Less Invasive Approach of Medial Meniscectomy in Rat: A Model to Target Early or Less Severe Human Osteoarthritis

Abstract

Objectives: The existing medial meniscectomy (MMx) procedure in rodents involves transection of MCL and wide opening of the knee capsule followed by meniscus transection that results into articular cartilage degeneration and causes significant changes in subchondral bone at specific post-MMx period. These animals serve as experimental osteoarthritis (OA) models. Structurally, knee is very complex. There may be a need to uncouple articular cartilage degenerative changes from subchondral bone degenerative changes in experimental OA models. Therapeutical drugs/agents, designed to treat articular cartilage degenerative changes of OA knee, may not be effective to treat subchondral bone degenerative changes or vice versa. The purpose of the study was to modify the existing MMx procedure to a less invasive procedure so that it causes only articular cartilage degenerative OA changes and no subchondral bone changes. This will serve as an early OA model to target degenerative changes in articular cartilage in human. Methods: Ten 8-9 weeks old male athymic nude rats underwent less invasive MMx on right knee; the left knee served as unoperated control. The surgery involved no transection of MCL and opening of knee capsule wide. The medial meniscus was pulled out from a slit made on the medial aspect of the knee capsule, and was transected. At 10 weeks post-MMx, animals were sacrificed and knees were assessed. Results: There was no significant alteration in bone strength parameters (BV/TV, Tb.Th, Tb.Sp, Tb.N, Tb.Pf, cortical wall thickness) in subchondral bone in the less invasive MMx knee as analyzed by μCT. X-ray radiography did not indicate the presence of any osteophyte at the knee margins. On the other hand, the less invasive MMx caused degenerative changes in articular cartilage as follows: fibrillation and thinning in the medial tibia; narrowing of medial knee joint; reduced proteoglycans shown by safranin-O staining; decreased metachromasia by PSR staining; alteration in collagen fibril thickness under cross-polarization light. Immunohistochemical expression was reduced (COL-II, aggrecan), increased (NITEGE, Col2-3/4m, COL-X, and MMP13) or imbalanced (lubricin) in articular cartilage thickness of less invasive MMx knee. Conclusion: The less invasive MMx procedure, in rat, can be a model for early or less severe human OA due to articular cartilage degenerative changes only and with no subchondral bone degenerative changes in the knee synovial joint. The therapeutical drugs/agents designed to repair articular cartilage may be suitable for this model and may lead to treatment of early or less severe human OA.