Structure and Function of Lubricin, the Glycoprotein Responsible for the Boundary Lubrication of Articular Cartilage

Swann, David A.

doi:10.1159/000406519

Cited by 76 publications

(99 citation statements)

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“…Our previous studies with normal bovine synovial fluids (4)(5)(6)(7)(8)(9) have shown that the ability of synovial fluid to act as a good lubricant depends on the presence of lubricin, a glycoprotein that is able to bind to articular cartilage and to act as a boundary lubricant. Lubricin is a minor component in bovine synovial fluid (5,6) and although we have been able to isolate a similar, if not identical, molecule from pooled human synovial fluids (22), the concentration of lubricin in individual fluid samples cannot be readily determined at the present time.…”

Section: Discussionmentioning

confidence: 99%

The lubricating activity of human synovial fluids

Swann¹,

Bloch²,

Swindell³

et al. 1984

Arthritis & Rheumatism

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The lubricating abilities of human synovial fluids were measured using a rotating cartilage-on-glass apparatus. A total of 247 human fluids were lubricationtested. Of these, 20 of the 180 knee fluids from patients with degenerativehaumatic joint disease lubricated less well than normal bovine synovial fluid. The remainder of the fluids from the knee and other joints were equivalent to normal bovine synovial fluid in their lubricating properties. The concentrations of hyaluronic acid, protein, and sialic acid and the relative viscosity of 117 human fluid samples were determined, but no relationships between the gross composition and the lubricating abilities were apparent.Several types of friction measuring devices have been used to measure the lubricating ability of synovial fluids, and a number of mechanisms by which synovial fluid lubricates articular cartilage have been suggested (1-3). Possibly a combination of mechanisms, working in concert, enables synovial fluid to function as a cartilage lubricant. The extent to which failure of one or more of these mechanisms may limit the lubricating functions of synovial fluid, and contribute to the occurrence of joint diseases, is not known.Our approach to the study of cartilage lubrication has been to fractionate synovial fluid by biochemical procedures and to determine which components are able to act as lubricants in a friction measuring device. In initial studies (4,5), an oscillating cartilageon-cartilage test system was used, and we were able to determine that a purified synovial fluid glycoprotein fraction was able to lubricate articular cartilage. More recently, a simplified rotating cartilage-on-glass friction measuring apparatus was used ( 6 ) . Solutions containing a single detectable glycoprotein (lubricin) (7) at concentrations as low as 30 pgiml had lubricating properties that were similar, if not identical, to those of whole synovial fluid. These results showed that lubricin was an extremely efficient lubricant for articular cartilage and indicated that lubricin was the component that endows synovial fluid with its boundary lubricating properties (8,9).The prior studies were all performed on bovine metacarpophalangeal synovial fluids. The present experiments were undertaken to obtain information about the lubricating ability of human synovial fluids by performing tests on pathologic samples using the rotating cartilage-on-glass test system. PATIENTS AND METHODSSynovial fluids. Human synovial fluids were obtained from patients seen at the Arthritis Unit at the Massachusetts General Hospital. Following the completion of clinical laboratory tests, the samples were stored at 4°C for variable lengths of time (1-4 days). The samples were clarified by

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Section: Discussionmentioning

confidence: 99%

The lubricating activity of human synovial fluids

Swann¹,

Bloch²,

Swindell³

et al. 1984

Arthritis & Rheumatism

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“…Lubricin, also known as superficial zone protein (SZP), megakaryocyte stimulating factor (MSF), hemangiopoietin (HAPO), or proteoglycan 4 (PRG4), has been found in a number of tissues, including synovial fluid, [1][2][3] superficial zone of cartilage, 4 synovial membrane, 5 tendon, 6 and meniscus, 7 as well as the urine of patients with aplastic anemia and of patients undergoing bone marrow transplantation during a period of acute thrombocytopenia. 8 Its best-known physical characteristic is its excellent boundary lubricating ability.…”

Section: Introductionmentioning

confidence: 99%

“…8 Its best-known physical characteristic is its excellent boundary lubricating ability. [1][2][3][9][10][11][12] It has the same lubricating properties as normal synovial fluid. [9][10][11][12] Lubricin also stimulates growth of megakaryocyte colonies in vitro.…”

Section: Introductionmentioning

confidence: 99%

Expression and mapping of lubricin in canine flexor tendon

et al. 2006

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Matrix composition and the biomechanical environment are intimately interdependent in most connective tissues. Lubricin has many distinct biological functions, including lubrication, antiadhesion, and cytoprotection in cartilage, tendons, and other tissues. This study investigated the distribution of lubricin in the canine flexor digitorum profundus (FDP) tendon by immunohistochemistry. Lubricin was found both on the tendon surface and at the interface of collagen fiber bundles within the tendon, where the cells are subjected to shear force in addition to tension and compression. The expression of lubricin in regions of the canine flexor tendon that differ in mechanical or nutritional environment was also investigated using RT-PCR. Six N-terminal splicing variants were identified from six distinct anatomical regions of flexor tendon. The variants with larger sizes were noted in regions subjected to significant shear and compressive forces. Lubricin is ubiquitous in the FDP tendon, with variations in distribution and splicing that appear to correspond to discrete anatomic locations that differ by mechanical or nutritional environment. ß

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“…Lubricin has been observed to lubricate a range of bearings, from latex-glass to cartilage-cartilage, in the boundary mode regime (18,(21)(22)(23), although the mechanism of lubrication is not fully understood. The investigation of the role of lubricin in cartilage lubrication is further complicated by a biphasic or pressure-mediated lubrication mecha-nism, which occurs when cartilage tissue is pressurized (24,25).…”

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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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Structure and Function of Lubricin, the Glycoprotein Responsible for the Boundary Lubrication of Articular Cartilage

Cited by 76 publications

References 0 publications

The lubricating activity of human synovial fluids

The lubricating activity of human synovial fluids

Expression and mapping of lubricin in canine flexor tendon

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

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