Increased accumulation of superficial zone protein (SZP) in articular cartilage in response to bone morphogenetic protein‐7 and growth factors

Khalafi, Afshin; Schmid, Thomas; Neu, Corey P.; Reddi, A. Hari

doi:10.1002/jor.20329

Cited by 89 publications

(86 citation statements)

References 52 publications

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“…This study provides new insight into the functional consequences of cytokine-mediated changes in lubricin metabolism reported previously (11,(27)(28)(29)(30)(31)(32). Changes in boundary mode eq (Figure 4) corresponded to previously demonstrated changes in lubricin localization induced by TGF␤1, IL-1␤, and OSM (27).…”

Section: Discussionsupporting

confidence: 84%

“…Bovine cartilage explants exposed in vitro to transforming growth factor ␤1 (TGF␤1) demonstrate an up-regulation of lubricin synthesis and surface localization (11,(27)(28)(29)(30)(31). In addition, TGF␤1 is known to mediate lubricin expression, which colocalizes to areas of low friction coefficient within the joint (32), while insulin-like growth factor 1, another potent anabolic signaling molecule in cartilage, does not affect lubricin metabolism and localization (28).…”

mentioning

confidence: 99%

“…In addition, TGF␤1 is known to mediate lubricin expression, which colocalizes to areas of low friction coefficient within the joint (32), while insulin-like growth factor 1, another potent anabolic signaling molecule in cartilage, does not affect lubricin metabolism and localization (28). Conversely, bovine explants treated with typical catabolic soluble factors, such as interleukin-1␣ (IL-1␣) (28), IL-1␤ (11,27,30), and tumor necrosis factor ␣ (TNF␣) (27,31), demonstrate a down-regulation of lubricin synthesis and tissue surface localization. IL-1␤ and TNF␣ have been found to be up-regulated in patients with unilateral anterior cruciate ligament injury (33) and in a rat model of antigen-induced arthritis (26), while lubricin expression is down-regulated and the friction coefficient is increased.…”

mentioning

confidence: 99%

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Alteration of articular cartilage frictional properties by transforming growth factor β, interleukin‐1β, and oncostatin M

Gleghorn¹,

Jones²,

Flannery³

et al. 2009

Arthritis & Rheumatism

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Objective. To evaluate the functional effects of transforming growth factor ␤1 (TGF␤1), interleukin-1␤ (IL-1␤), and oncostatin M (OSM) on the frictional properties of articular cartilage and to determine the role of cytokine-mediated changes in cartilage frictional properties by extracting and redepositing lubricin on the surface of cartilage explants.Methods. Neonatal bovine cartilage explants were cultured in the presence or absence of 10 ng/ml of TGF␤1, IL-1␤, or OSM over 48 hours. Boundary lubrication tests were conducted to determine the effects of endogenously produced surface localized lubricin and of exogenous lubricin at the tissue surface and in the lubricant solution. The initial friction coefficient ( 0 ), equilibrium friction coefficient ( eq ), and Young's modulus (E Y ) were determined from the temporal load data.Results. IL-1␤ and OSM decreased tissue glycosaminoglycan (GAG) content by ϳ20% over 48 hours and decreased E Y to a similar extent (11-17%), but TGF␤ did not alter GAG content or E Y . Alterations in proteoglycan content corresponded to changes in 0 , but endogenous lubricin decreased boundary mode eq . The addition of exogenous lubricin, either localized at the tissue surface or in the lubricating solution, did not modulate 0 , but it did lower eq in cytokine-treated cartilage.Conclusion. This study provides new insight into the functional consequences of cytokine-mediated changes in friction coefficient. In combination with established pathways of cytokine-mediated lubricin metabolism, these data provide evidence of distinct biochemical origins of boundary and biphasic pressuremediated lubrication mechanisms in cartilage, with boundary lubrication regulated by surface accumulation of lubricants and biphasic lubrication controlled by factors such as GAG content that affect water movement through the tissue.

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Section: Discussionsupporting

confidence: 84%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Alteration of articular cartilage frictional properties by transforming growth factor β, interleukin‐1β, and oncostatin M

Gleghorn¹,

Jones²,

Flannery³

et al. 2009

Arthritis & Rheumatism

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“…Surface zone of bovine articular cartilage was obtained from the calf knee joint as described previously in our lab by Khalafi et al [13]. The bovine articular cartilage was divided into three zones (surface, middle and deep).…”

Section: Harvest Of Bovine Articular Cartilage and Isolation Of The Cmentioning

confidence: 99%

Identification of superficial zone articular chondrocyte stem/progenitor cells

Hattori¹,

Oxford²,

Reddi³

2007

Biochemical and Biophysical Research Communications

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119

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Identification of progenitor/stem cell populations that differentiate specifically towards superficial zone articular chondrocytes is an unmet challenge for cartilage tissue engineering. Using fluorescence activated cell sorting (FACS) analysis we found a characteristic pattern of "side population" (SP) stem cells identified by the Hoechst33342 dye. We established micromass cultures from this population of cells and tested their chondrogeneic potential. Control (untreated) cultures were minimally stained for alcian blue-a marker of chondrogenesis. However, with BMP-7 treatment, alcian blue staining was increased. Superficial zone protein-a specific marker for articular cartilage superficial zone chondrocytes-increased with BMP-7 and/or TGF-β1 treatment in SP micromass cultures. Our results demonstrate the presence of stem/progenitor cells in the SP fraction isolated from the surface zone of bovine cartilage and have the ability to specifically differentiate towards the superficial zone articular chondrocyte.

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“…17,18 Previous research in cell culture demonstrated that the level of SZP secreted into the media can be controlled by applying different cytokines. 19 Anabolic cytokines and growth factors (e.g., TGF-b family members) increase the expression of SZP, while catabolic cytokines (e.g., IL-1b) decrease the expression and accumulation of SZP. 17,19 Differences in the friction coefficient at regions of the articular cartilage surface with distinct SZP protein levels motivated the investigation of the effect of changes in the SZP expression level due to cytokine treatment on the coefficient of friction.…”

mentioning

confidence: 99%

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

DuRaine

Neu

Chan

et al. 2008

Journal Orthopaedic Research

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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-b1 and IL-1b 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-b1 or IL-1b) 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-b1 and IL-1b 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-b1 treatment corresponded to increased depth of SZP staining within the superficial zone, while friction coefficient changes due to the IL-1b treatment were independent of SZP depth of staining. However, the changes induced by the IL-1b 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-b1 and IL-1b treatment and that the friction coefficient depends on multiple factors, including SZP localization and surface roughness. ß

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Increased accumulation of superficial zone protein (SZP) in articular cartilage in response to bone morphogenetic protein‐7 and growth factors

Cited by 89 publications

References 52 publications

Alteration of articular cartilage frictional properties by transforming growth factor β, interleukin‐1β, and oncostatin M

Alteration of articular cartilage frictional properties by transforming growth factor β, interleukin‐1β, and oncostatin M

Identification of superficial zone articular chondrocyte stem/progenitor cells

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

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