Regulation of the friction coefficient of articular cartilage by TGF-β1 and IL-1β

Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, University of California, Davis, Medical Center, Sacramento, CA 95817, USA.
Journal of Orthopaedic Research (Impact Factor: 2.99). 02/2009; 27(2):249-56. DOI: 10.1002/jor.20713
Source: PubMed


Articular cartilage functions to provide a low-friction surface for joint movement for many decades of life. Superficial zone protein (SZP) is a glycoprotein secreted by chondrocytes in the superficial layer of articular cartilage that contributes to effective boundary lubrication. In both cell and explant cultures, TGF-beta1 and IL-1beta have been demonstrated to, respectively, upregulate and downregulate SZP protein levels. It was hypothesized that the friction coefficient of articular cartilage could also be modulated by these cytokines through SZP regulation. The friction coefficient between cartilage explants (both untreated and treated with TGF-beta1 or IL-1beta) and a smooth glass surface due to sliding in the boundary lubrication regime was measured with a pin-on-disk tribometer. SZP was quantified using an enzyme-linked immunosorbant assay and localized by immunohistochemistry. Both TGF-beta1 and IL-1beta treatments resulted in the decrease of the friction coefficient of articular cartilage in a location- and time-dependent manner. Changes in the friction coefficient due to the TGF-beta1 treatment corresponded to increased depth of SZP staining within the superficial zone, while friction coefficient changes due to the IL-1beta treatment were independent of SZP depth of staining. However, the changes induced by the IL-1beta treatment corresponded to changes in surface roughness, determined from the analysis of surface images obtained with an atomic force microscope. These findings demonstrate that the low friction of articular cartilage can be modified by TGF-beta1 and IL-1beta treatment and that the friction coefficient depends on multiple factors, including SZP localization and surface roughness.

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    • "In articular chondrocytes, TGF-β1 mediates cell survival and matrix synthesis [21]. This factor has been shown to play a key role in maintenance of chondrocyte phenotype, lubricating properties, and chondrocyte response to mechanical loading [22-24]. Exogenous application of TGF-β1 at 10 ng/ml to self-assembled primary articular chondrocytes increased the GAG content and compressive properties [13]; in fibrochondrocytes, it was shown to increase both the collagen and GAG content along with mechanical properties [25]. "
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    ABSTRACT: Costochondral cells may be isolated with minimal donor site morbidity and are unaffected by pathologies of the diarthrodial joints. Identification of optimal exogenous stimuli will allow abundant and robust hyaline articular cartilage to be formed from this cell source. In a three factor, two level full factorial design, the effects of hydrostatic pressure (HP), transforming growth factor beta1 (TGF-beta1), and chondroitinase ABC (C-ABC), and all resulting combinations, were assessed in third passage expanded, redifferentiated costochondral cells. After 4 wks, the new cartilage was assessed for matrix content, superficial zone protein (SZP), and mechanical properties. Hyaline articular cartilage was generated, demonstrating the presence of type II collagen and SZP, and the absence of type I collagen. TGF-beta1 upregulated collagen synthesis by 175% and glycosaminoglycan synthesis by 75%, resulting in a nearly 200% increase in tensile and compressive moduli. C-ABC significantly increased collagen content, and fibril density and diameter, leading to a 125% increase in tensile modulus. Hydrostatic pressure increased fibril diameter by 30% and tensile modulus by 45%. Combining TGF-beta1 with C-ABC synergistically increased collagen content by 300% and tensile strength by 320%, over control. No significant differences were observed between C-ABC/TGF-beta1 dual treatment and HP/C-ABC/TGF-beta1. Employing biochemical, biophysical, and mechanical stimuli generated robust hyaline articular cartilage with a tensile modulus of 2 MPa and a compressive instantaneous modulus of 650 kPa. Using expanded, redifferentiated costochondral cells in the self-assembling process allows for recapitulation of robust mechanical properties, and induced SZP expression, key characteristics of functional articular cartilage.
    Full-text · Article · Dec 2013 · Arthritis research & therapy
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    • "Cartilage explants were completely immersed in 10 mL of PBS throughout the duration of testing to maintain tissue hydration. Prior to the initiation of testing, each explant was allowed to equilibrate [23] for 2 min under the applied normal load [19] [24]. Data were acquired in 0.1 s intervals for 60 min using Labview (National Instruments, Austin, TX). "
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    ABSTRACT: Friction and wear of four common orthopaedic biomaterials, alumina (Al2O3), cobalt-chromium (CoCr), stainless steel (SS), and crosslinked ultra-high-molecular-weight polyethylene (UHMWPE), sliding against bovine articular cartilage explants were investigated by reciprocating sliding, nanoscale friction and roughness measurements, protein wear assays, and histology. Under the experimental conditions of the present study, CoCr yielded the largest increase in cartilage friction coefficient, largest amount of protein loss, and greatest change in nanoscale friction after sliding against cartilage. UHMWPE showed the lowest cartilage friction coefficient, least amount of protein loss, and insignificant changes in nanoscale friction after sliding. Although the results are specific to the testing protocol and surface roughness of the examined biomaterials, they indicate that CoCr tends to accelerate wear of cartilage, whereas the UHMWPE shows the best performance against cartilage. This study also shows that the surface characteristics of all biomaterials must be further improved to achieve the low friction coefficient of the cartilage/cartilage interface. [DOI: 10.1115/1.4004760]
    Full-text · Article · Oct 2011 · Journal of Tribology
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    • "This increased expression of lubricin in OA chondrocytes may, somehow, be related to the absence of cytokines, which seem to influence lubricin biosynthesis. A disregulation of lubricin metabolism, under the influence of elevated cytokine concentrations in diseased or damaged joints, has been described,14,38–40 and this, in time, might thereby lead to lubrication deficiencies and loss of function. In this respect, it has been claimed that a decrease in synovial fluid lubricin concentrations following anterior cruciate ligament injury may place the joint at an increased risk of wear-induced damage, as a consequence of lack of boundary lubrication, potentially leading to secondary osteoarthritis. "
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    ABSTRACT: Osteoarthritis (OA) is characterized by degenerative changes within joints that involved quantitative and/or qualitative alterations of cartilage and synovial fluid lubricin, a mucinous glycoprotein secreted by synovial fibroblasts and chondrocytes. Modern therapeutic methods, including tissue-engineering techniques, have been used to treat mechanical damage of the articular cartilage but to date there is no specific and effective treatment. This study aimed at investigating lubricin immunohistochemical expression in cartilage explant from normal and OA patients and in cartilage constructions formed by Poly (ethylene glycol) (PEG) based hydrogels (PEG-DA) encapsulated OA chondrocytes. The expression levels of lubricin were studied by immunohistochemistry: i) in tissue explanted from OA and normal human cartilage; ii) in chondrocytes encapsulated in hydrogel PEGDA from OA and normal human cartilage. Moreover, immunocytochemical and western blot analysis were performed in monolayer cells from OA and normal cartilage. The results showed an increased expression of lubricin in explanted tissue and in monolayer cells from normal cartilage, and a decreased expression of lubricin in OA cartilage. The chondrocytes from OA cartilage after 5 weeks of culture in hydrogels (PEGDA) showed an increased expression of lubricin compared with the control cartilage. The present study demonstrated that OA chondrocytes encapsulated in PEGDA, grown in the scaffold and were able to restore lubricin biosynthesis. Thus our results suggest the possibility of applying autologous cell transplantation in conjunction with scaffold materials for repairing cartilage lesions in patients with OA to reduce at least the progression of the disease.
    Full-text · Article · Sep 2011 · European journal of histochemistry: EJH
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