Muscular loading of joints triggers cellular secretion of PRG4 into the joint fluid

Abstract

We developed a novel testing system that allows quantification of joint loading and permits analysis of changes in total protein and PRG4 contents in joint fluid of intact knees in live mice. A sequence of 15 repeat, isometric muscular contractions of "low" intensity (less than 50% of the maximal isometric muscular force), and "high" intensity (greater than 55% of maximal) were applied repeatedly (up to five times with a 15 min rest between contractions) to the mouse knee. Increases in knee joint loading were accompanied with significant increases in total protein (p<0.0001) and PRG4 concentrations in the synovial fluid. Total protein and PRG4 concentrations decreased with repeated "high" intensity loading. However, the addition of cell secretion inhibitors to the knee prior to muscular loading resulted in PRG4 levels that remained below the detection limit for all loading conditions. These results suggest that changes in synovial fluid proteins and PRG4 concentrations upon joint loading are mediated by cells within the joint, and that these changes may be used as quantitative indicators for the intensity and duration of acute joint loading, and might serve as a powerful clinical tool to assess the effectiveness of rehabilitation and prevention exercise programs.

The effect of vigorous running and cycling on serum COMP, lubricin, and femoral cartilage thickness: a pilot study

“…The increase in serum lubricin and COMP following acute vigorous cycling and running exercise in healthy humans in the current study are consistent with reports of increased PRG-4 and COMP production in response to mechanical load in cartilage explants and animal models (Piscoya et al 2005;Nugent-Derfus et al 2007;Abusara et al 2013). The increase in serum COMP in the present study is also consistent with several studies that have previously demonstrated that serum COMP increases following exercise (Neidhart et al 2000;Kersting et al 2005;Niehoff et al 2011).…”

“…This may also explain why exercise has previously been shown to improve symptoms such as knee joint stiffness and pain among individuals with joint disease (O'Reilly et al 1999). Interestingly, several in vivo animal studies have recently demonstrated that lubricin expression is attenuated under conditions associated with high levels of joint loading, including repeated high intensity exercise and with abnormal loading (Ni et al 2012;Elsaid et al 2012;Abusara et al 2013). Therefore, due to the high impacted loading associated with running loads compared to cyclists we postulated that runners might demonstrate reduced resting lubricin concentrations.…”

“…Several in vivo animal studies have provided evidence to suggest that lubricin synthesis is downregulated in degenerative joints (Abusara et al 2013), following anterior cruciate ligament injury (Elsaid et al 2012) and in a meniscectomy-induced OA model (Young et al 2006). In contrast, low to moderate mechanical loading has been shown to significantly increase lubricin expression and is associated with fewer degenerative changes (Ni et al 2012).…”

Proteoglycan 4 is a diagnostic biomarker for COPD

“…Repeated high-intensity muscular loading reduces PRG4 concentrations. 7 The difficulty of muscle movement during breathing could be associated with lung function decline in COPD patients. Additionally, long-term corticosteroid inhalation partially modulated the pulmonary composition of the extracellular matrix, affecting, for example, the level of proteoglycan in moderate-to-severe COPD.…”

The diagnostic value of proteoglycan 4 in the differentiation of stable and exacerbation periods in chronic obstructive pulmonary disease: a preliminary study

“…ISSN 0970-938X www.biomedres.info pathologies. In various studies, Proteoglycan-4 (PRG4) has been found in several organs such as the lung, heart, liver, bone, and cartilage and has several biological functions such as immunoreactivity, cytoprotection, lubrication, and matrix binding [5][6][7].…”