Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury

Elsaid, Khaled A.; Fleming, Braden C.; Oksendahl, HL; Machan, Jason T.; Pd, Fadale; Mj, Hulstyn; Shalvoy, Robert M.; Jay, Gregory D.

doi:10.1002/art.23495

Cited by 234 publications

(277 citation statements)

References 25 publications

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“…Common traumatic knee injuries, such as anterior cruciate ligament tears, are strong risk factors for the development of OA. Lubricin levels in SF decrease after anterior cruciate ligament injury and can take up to a year to return to baseline values (40). Several studies have demonstrated a disease-modifying effect for the intraarticular injection of native or recombinantly expressed lubricin in rodent models of posttraumatic OA (28,29,41,42).…”

Section: Discussionmentioning

confidence: 99%

“…HSF was aspirated from the uninjured contralateral joints of patients with an anterior cruciate ligament injury (n = 4). These samples were obtained without lavage just before reconstructive surgery (40). Other HSFs were aspirated from knee joints of postmortem donors with no OA within 12 h of death (two male donors; ages, 29 and 39; National Disease Research Interchange).…”

Section: Methodsmentioning

confidence: 99%

“…Lyophilized HSL was obtained from SBH Sciences and has been characterized previously (41,42). This product was solubilized using distilled water to a concentration of 250 μg/ mL, which is the estimated lubricin concentration in SF (40). SF from patients with CACP (CACP-SF) was obtained from patients in the years between 2000 and 2011, following diagnostic knee joint aspiration (n = 4).…”

Section: Methodsmentioning

confidence: 99%

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Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis

Waller

Zhang

Elsaid

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

217

179

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Osteoarthritis is a complex disease involving the mechanical breakdown of articular cartilage in the presence of altered joint mechanics and chondrocyte death, but the connection between these factors is not well established. Lubricin, a mucinous glycoprotein encoded by the PRG4 gene, provides boundary lubrication in articular joints. Joint friction is elevated and accompanied by accelerated cartilage damage in humans and mice that have genetic deficiency of lubricin. Here, we investigated the relationship between coefficient of friction and chondrocyte death using ex vivo and in vitro measurements of friction and apoptosis. We observed increases in whole-joint friction and cellular apoptosis in lubricin knockout mice compared with wild-type mice. When we used an in vitro bovine explant cartilage-on-cartilage bearing system, we observed a direct correlation between coefficient of friction and chondrocyte apoptosis in the superficial layers of cartilage. In the bovine explant system, the addition of lubricin as a test lubricant significantly lowered the static coefficient of friction and number of apoptotic chondrocytes. These results demonstrate a direct connection between lubricin, boundary lubrication, and cell survival and suggest that supplementation of synovial fluid with lubricin may be an effective treatment to prevent cartilage deterioration in patients with genetic or acquired deficiency of lubricin.camptodactyly-arthropathy-coxa vara-pericarditis | shear strain | antiadhesion | tribology

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis

Waller

Zhang

Elsaid

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

217

179

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“…5 Cytokines have been shown to be involved in a number of arthritic disorders such as haemarthrosis, 6 osteoarthritis (OA), 7,8 rheumatoid arthritis (RA), [9][10][11][12][13] inflammatory arthritis 14 and acute joint trauma. [15][16][17][18][19][20][21] The pro-inflammatory cytokines, IL-1b, IL-6 and TNF-a, are considered major players in both RA and OA. 7,9,10,12,22 In addition, other cytokines such as IL-8, IL-15, IL-17, IL-18 and IL-21 have been described as being involved in both OA and RA, 7,10,11,[22][23][24][25][26] albeit at different levels; synovial fluid cytokine levels are in general significantly increased in patients with RA compared to patients with OA.…”

mentioning

confidence: 99%

Buprenorphine does not impact the inflammatory response in haemophilia A mice with experimentally-induced haemarthrosis

et al. 2014

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Haemarthrosis is the most common clinical manifestation of haemophilia and is responsible for significant morbidity in haemophilic patients. The murine experimentally-induced knee bleeding model is an important model in haemophilia research but it is currently unknown if the use of analgesia in this model might impact on the inflammatory response. The aim was to investigate the inflammatory response after a needle induced knee bleed in haemophilia A mice treated with buprenorphine or saline. One hundred and sixty mice were randomized into two groups to blindly receive buprenorphine or saline. All the mice were anaesthetized and knee injury was induced by inserting a 30 G needle into the right knee joint. At t ¼ 6, 24, 48 and 72 h, 20 mice from each group were terminated and the following parameters were assessed: change in body weight and joint diameter, visual bleeding score (VBS), white blood counts, haematocrit, platelet concentrations, haemoglobin, plasma haptoglobin and plasma and synovial fluid levels of 23 cytokines. Twenty mice were terminated at t ¼ 0 receiving no injury or treatment to provide baseline measures. Twenty-one cytokines in plasma and 22 cytokines in synovial fluid, joint diameter change, VBS and blood parameters were not significantly altered by the administration of buprenorphine. Slight alterations of plasma haptoglobin at t ¼ 48 h, body weight, plasma and synovial eotaxin and plasma G-CSF were found in buprenorphine-treated mice. We demonstrated that buprenorphine does not overall impact on the inflammatory response, and the use of buprenorphine in the knee bleeding model in haemophilic mice should be continued.

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“…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%

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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Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury

Cited by 234 publications

References 25 publications

Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis

Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis

Buprenorphine does not impact the inflammatory response in haemophilia A mice with experimentally-induced haemarthrosis

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

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