Attachment of cartilage wear particles to the synovium negatively impacts friction properties
Introduction
The function of synovial joints under repeated loading throughout life is supported by lubricating synovial fluid (SF) and the unique tribological properties of cartilage and synovium. As the main load-bearing tissue, articular cartilage can withstand compressive forces while also maintaining low friction properties, allowing the repeated sliding contact between opposing surfaces during locomotion to occur with minimal tissue wear. These friction properties of cartilage have been characterized at the tissue level with loading devices for both intact joints (Unsworth et al., 1975) and explanted cartilage tissues (Wang and Ateshian, 1997, Krishnan et al., 2004, Basalo et al., 2005, Krishnan et al., 2005, Basalo et al., 2006, Basalo et al., 2007, Carter et al., 2007, Caligaris and Ateshian, 2008, Oungoulian et al., 2014), and at the molecular scale utilizing atomic force microscopy (Park et al., 2004, Kienle et al., 2015). Further work has identified mechanisms that dictate the frictional interactions between articular surfaces such as lubrication by fluid film, boundary, and interstitial fluid pressurization phenomena (Ateshian and Mow, 2005).
While cartilage plays the main load-bearing role in the joint, frictional interactions occur between any tissues in direct contact during articulation. The synovium, as the membrane encapsulating the joint space, would thus interact with underlying cartilage surfaces and with itself in regions where the tissue folds. Similar to cartilage, the frictional properties of the synovium may have important implications for tissue level wear over a lifetime of repeated loading. We have previously demonstrated that fibroblast-like synoviocytes residing on the intimal layer of the synovium are mechanosensitive, responding to fluid-induced shear stress as generated by redistribution of the synovial fluid during articulation (Estell et al., 2017). Similarly, frictional interactions in areas of direct contact with underlying tissues may provide mechanical stimulus to resident cells within the synovium. Thus, the frictional properties of the synovium are of interest in understanding joint homeostasis with respect to tissue tribology as well as cellular mechanotransduction.
Early work described friction coefficients for synovium in contact with glass that are comparative to those for cartilage, and provide insight into the important role of synovial fluid as a lubricant (Radin et al., 1971, Cooke et al., 1976). The present study seeks first to expand on this characterization by employing a custom testing device to address the hypothesis that synovium friction coefficients on biologically relevant counterfaces (cartilage or other synovium) are comparably low to cartilage, and to explore the dependence of friction coefficient on time, load, and lubricant to further elucidate mechanisms at play.
As a decrease in the lubricating capacity of synovial fluid is a hallmark of the osteoarthritic (OA) environment (Kosinska et al., 2015, Szychlinska et al., 2016), friction measurements utilizing different lubricating baths can provide useful information to define the contribution of synovial fluid to friction properties. While an increase in the friction coefficient of synovium during OA has not been reported, we may infer that it is negatively affected by the decrease in synovial fluid lubricating properties and worsening friction properties of underlying cartilage as it degrades and surface roughness increases (Basalo et al., 2006, Szychlinska et al., 2016). In cartilage, increased friction during OA leads to chondrocyte apoptosis (Neu et al., 2010, Waller et al., 2012), while shear stress regulates expression and accumulation of lubricating proteins at the superficial zone (Neu et al., 2007). Tissue mechanical properties such as substrate stiffness have been shown to affect cell function, and specifically calcium signaling in response to mechanical stimuli (Kim et al., 2009, Derricks et al., 2015). Thus, in OA, increased friction could result in elevated tissue wear as well as overloading of the mechanosensitive cells residing in the synovium.
Beyond a decrease in synovial fluid lubricating properties, the generation of cartilage wear particles (CWP) by mechanical and chemical degradation of the articular surfaces during OA may also negatively impact synovium friction properties. These wear particles are released into the synovial fluid and have been observed in animal and clinical samples, attached directly to the synovial intima (Lloyd Roberts, 1953). Synovial fluid aspirates from healthy and OA patients have shown a correlation between increasing number, size, and roughness of CWP and grade of OA (Podsiadlo et al., 1997, Kuster et al., 1998). In vivo animal studies have demonstrated that CWP can initiate progression of OA, whereby injection of CWP into lapine, canine, and equine knees have all shown a rapid development of synovitis followed by onset of fibrotic thickening of the synovium and decreased cartilage thickness, similar to traditional animal models of OA (Chrisman et al., 1965, Evans et al., 1984, Kuroki et al., 2011). Our group has also demonstrated in animal and human models that small CWP (<10 µm) both attach to the cell membrane of fibroblast-like synoviocytes and become phagocytosed, and directly influence cell functions such as proliferation and production of proteinase, collagen, and nitric oxide (Silverstein et al., 2017a, Silverstein et al., 2017b, Estell et al., 2019). The present study explores the degradation of synovium friction properties in the OA environment by testing the hypothesis that CWP attachment to the tissue surface increases friction coefficient. It is anticipated that these findings will contribute to future work elucidating the relationship between tissue-level mechanical properties and mechanotransduction of resident cells, and how this influences the contribution of these cells to disease progression in OA.
Section snippets
Explant culture and wear particle treatment
Juvenile bovine synovium and cartilage explants were harvested from calf knees and maintained in DMEM supplemented with 1% PSAM, 1% ITSTM + Premix (BD Biosciences, San Jose, CA), 100 mg/mL sodium pyruvate (Sigma-Aldrich, St. Louis, MO), and 50 mg/mL L-proline (Sigma-Aldrich). Cartilage wear particles (CWP) were generated from explants submerged in sterile PBS and manually abraded with waterproof 120-grit sandpaper (McMaster-Carr, Elmhurst, IL) as previously described (Silverstein et al., 2017a
Results
As in earlier studies, initial friction measurements utilized a glass counterface to establish properties of the synovium explant itself and explore the effect of load and lubricant bath on friction coefficient as a function of time throughout the test. In this setup, differing contact pressures and lubricant baths produced distinct patterns of time-dependence in friction coefficient. In synovial fluid (SF), a markedly low and constant friction coefficient was observed at low contact pressure
Discussion
In situ experiments with intact joints have demonstrated a link between articulation and synovial fluid composition (Ingram et al., 2008), while in vitro work has shown that specific mechanical stimuli such as stretch-induced strain (Momberger et al., 2005, Momberger et al., 2006) and fluid-induced shear stress (Yanagida-Suekawa et al., 2013) modulate key synoviocyte functions like lubricant production. Together these findings suggest that mechanotransduction contributes to joint homeostasis,
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work was funded in part by the Orthopedic Scientific Research Foundation (02-2015), NIH 1R01AR068133, and T32AR059038.
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