A Model System of the Dynamic Loading Occurring in Synovial Joints: The Biological Effect of Plowing on Pristine Cartilage

Abstract

Mechanical stress is listed as a main risk factor for cartilage degradation. The aim of this study was to investigate the biological response of cartilage to dynamic loading such as plowing. Cartilage strips harvested from bovine nasal septum were submitted to plowing using a cylindrical indenter, applying a constant normal force in the vertical axis and moving at constant speed in the horizontal axis. After plowing, cell viability, gene expression and glycosaminoglycan (GAG) release were measured with conventional assays. The cell-viability assay and qRT-PCR showed that plowing induces cell death and matrix metalloproteinase 3 (MMP-3) upregulation. The addition of actinomycin D, before or after plowing, confirmed that plowing was responsible for the observed MMP-3 upregulation. Even if the transcriptions of the tissue inhibitor of metalloproteinase (TIMP-1), aggrecan (Agg), collagen type I (Coll1), collagen type II (Coll2) and fibronectin (Fn) were not significantly affected by plowing, actinomycin D treatment revealed that plowing induces a strong increase in TIMP-1 and Coll1 messenger RNA content and influences the gene regulation of Agg, Coll2 and Fn. Furthermore, plowed cartilage explants exhibited enhanced GAG release. Application of hydroxamate MMP inhibitor after loading showed that plowing induces GAG release via the activation of catabolic enzymes. Plowing causes cell death of the chondrocytes closer to the surface as well as matrix damage, observed as GAG loss. Moreover, in healthy chondrocytes, plowing promotes the production and activation of catabolic enzymes like MMP-3.

Jaw closing movement and sex differences in temporomandibular joint energy densities

“…The molecular biological perspectives of TMJ loading should also be considered . Mechanical loads, in a dose‐dependent manner with respect to magnitude, frequency and duration, inhibit or promote molecular events responsible for cartilage health or destruction, including the synthesis of inflammatory mediators . Excessive loading and the consequent inflammatory mediators are associated with increased Wnt signalling in the superficial zone of TMJ fibrocartilage and loss of fibrocartilage stem cells in this zone .…”

“…Comparison of component variables that contribute to temporomandibular joint (TMJ) energy densities between females and males during jaw closure from laterotrusion, where * indicates significant difference of inflammatory mediators [27][28][29]. Excessive loading and the consequent inflammatory mediators are associated with increased Wnt signalling in the superficial zone of TMJ fibrocartilage and loss of fibrocartilage stem cells in this zone 30.…”

Articular cartilage response to a sliding load using two different-sized spherical indenters 1

“…Forces within a physiological range are associated with normal ECM turnover and an effort of the chondrocytes to adapt the ECM in response to the loading conditions [4,5]. On the other hand, non-physiological forces have been shown to lead to ECM damage that manifests itself in proteoglycan (PG) loss and collagen fiber disruption [6] and an increase in catabolic enzymes such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS') [7][8][9][10]. Also, the increase in other proteins that are associated with degenerative changes of the ECM have been reported, such as fibronectin and cartilage oligomeric matrix protein (COMP) [11][12][13].…”

Cartilage Biomechanical and Mechanobiological Response to Sliding Contact

“…Therefore, incorporating in vitro loading protocols that ensure fluid flow within the entire tissue and not only through the lateral boundaries would better reproduce the in vivo physiological condition as well as CPM condition. However, only a few in vitro studies have attempted to study cartilage mechanobiology under physiological loading conditions in which fluid flow is permitted through the entire cartilage surface (Correro-Shahgaldian et al, 2014;Schätti et al, 2015Schätti et al, , 2016. Detailed discussion of these studies and the associated testing apparatuses is provided in Chapter 3.…”

“…Briefly, important aspects of the physiological conditions within the synovial joints such as strain level, stroke length, specimen source were ignored in those studies. For example, Correro-Shahgaldian et al (2014) have investigated the effect of plowing on the biological response of cartilage using specimens harvested from bovine nasal septum (BNS) which is not a load-bearing cartilage. Also, Schätti et al (2015,2016) studied the effect of surface relative motion during sliding on the mechanobiology of cartilage using bovine condyles.…”