Effects of in vivo cyclic compressive loading on the distribution of local Col2 and superficial lubricin in rat knee cartilage

Abstract

This study aimed to examine the effects of an episode of in vivo cyclic loading on rat knee articular cartilage (AC) under medium‐term observation, while also investigating relevant factors associated with the progression of post‐traumatic osteoarthritis (PTOA). Twelve‐week‐old Wistar rats underwent one episode comprising 60 cycles of 20 N or 50 N dynamic compression on the right knee joint. Spatiotemporal changes in the AC after loading were evaluated using histology and immunohistochemistry at 3 days and 1, 2, 4, and 8 weeks after loading (n = 6 for each condition). Chondrocyte vitality was assessed at 1, 3, 6, and 12 hours after loading (n = 2 for each condition). A localized AC lesion on the lateral femoral condyle was confirmed in all subjects. The surface and intermediate cartilage in the affected area degenerated after loading, but the calcified cartilage remained intact. Expression of type II collagen in the lesion cartilage was upregulated after loading, whereas the superficial lubricin layer was eroded in response to cyclic compression. However, the distribution of superficial lubricin gradually recovered to the normal level 4 weeks after loading‐induced injury. We confirmed that 60 repetitions of cyclic loading exceeding 20 N could result in cartilage damage in the rat knee. Endogenous repairs in well‐structured joints work well to rebuild protective layers on the lesion cartilage surface, which may be the latent factor delaying the progression of PTOA.

A VCP modulator, KUS121, as a promising therapeutic agent for post-traumatic osteoarthritis

“…This study has several limitations. First, the cyclic loading model used in this study in rat is not able to produce PTOA-like changes in the whole joint 33 . Although the current animal model was adequate to achieve the purpose of this study to examine protective effect of KUS121 on the suppression of acute chondrocyte death, one of the crucial early events in OA, other OA models would be needed to evaluate the effect of KUS121 on whole joint OA changes.…”

“…Rats were intraperitoneally administered a combination anaesthetic containing 0.375 mg/kg medetomidine, 2 mg/kg midazolam, and 2.5 mg/kg butorphanol, and were randomly assigned into vehicle-or KUS121-treated groups (6 rats per group). The cartilage injury was exposed by cyclic compression as previously reported 33 . Briefly, each right knee was placed in a prone position on a custom-made table with the knee at approximately 140° flexion and subjected to cyclic compressive loading including a pre-load of 5 N, peak load of 20 N with an approaching speed of 1 mm/s, and a 10 s rest interval.…”

“…To assess the intensity of Safranin O staining at the cartilage lesions, the RGB images of each section were split to Red (R), Green (G) and Blue (B) channels using ImageJ software. Among them, the Red images inverted 8-bit grayscale, and the relative intensity in lesion area was calculated by dividing by the intensity in growth plate 33,36 . To evaluate synovitis in the knee joints, the Haematoxylin and eosin stained sections were graded according to the synovitis inflammatory score as previously reported by Jackson et al 37 .…”

Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage

“…Furthermore, the cartilage explants displayed an increased coefficient of friction demonstrating that injurious load significantly compromises tissue function [168]. Application of 60 cycles of injurious compressive load (20 and 50 N) on rat knees in vivo resulted in a transient reduction in lubricin within the lesions that formed on the lateral femoral condyles [169]. The detrimental effects of high-magnitude, high-strain-rate injurious loading regimens are thought to result as a consequence of cellular damage, such as chondrocyte apoptosis and necrosis [170].…”

One session of 20 ​N cyclic compression induces chronic knee osteoarthritis in rats: A long-term study

“…One session of cyclic compression, with a peak load of 20 ​N and 60 cycles, was applied to the rat's knee [ 9 ]. We demonstrated that this one-session cyclic compression could lead to regional cytopenia and loss of glycosaminoglycan (GAG), which is an important functional component of the extracellular matrix (ECM) [ 15 ], and simultaneously, to no immediate structural damage. However, we did not observe further OA pathological progression of OA 8 weeks after compression.…”