Superficial Zone Protein (Lubricin) in the Different Tissue Compartments of the Knee Joint: Modulation by Transforming Growth Factor Beta 1 and Interleukin-1 Beta

Lee, Sang Yang; Niikura, Takahiro; Reddi, A. Hari

doi:10.1089/ten.tea.2007.0367

Cited by 58 publications

(56 citation statements)

References 42 publications

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“…To the knowledge of the authors, this is the first report of lubricin surface staining of the human ACL sheath, although surface lubricin has been previous found in bovine ACLs and PCLs. 14 The distribution of lubricin in the intact human meniscus, along both the femoral and tibial surfaces as well as ECM and IC, is in accordance with previous findings 14, 15 The finding of lubricin in the intact human ACL, meniscus, and acetabular labrum (data not shown) suggests that lubricin should not be associated with articular cartilage or synovial fluid alone, but rather should be thought of as an abundant, global lubricating protein in synovial joints.…”

Section: Discussionsupporting

confidence: 89%

“…8 Collectively, these homologous glycoproteins have been referred to as proteoglycan 4 and are encoded by 12 exons of the gene msf, also known as Prg4. 10 Possessing lubricating 11 and anti-adhesive properties, 12 lubricin has been reported in canine anterior cruciate and lateral collateral ligaments, 13 bovine anterior and posterior cruciate ligaments, 14 and bovine menisci. 14,15 The presence of lubricin among fascicles of collagen fibers in caprine 16 and human 4 tendons as well as bovine ligaments 14 suggested a role in interfascicular tribology.…”

mentioning

confidence: 99%

“…14,15 The presence of lubricin among fascicles of collagen fibers in caprine 16 and human 4 tendons as well as bovine ligaments 14 suggested a role in interfascicular tribology. Immunohistochemical localization of lubricin within cells in the bovine knee compartment 14 suggests local synthesis of this glycoprotein. The previous finding of lubricin on the ruptured surface of human supraspinatus and biceps tendons 17 raises questions regarding the distribution of lubricin within the human torn ACL and meniscus and its effects on healing.…”

mentioning

confidence: 99%

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Lubricin distribution in the torn human anterior cruciate ligament and meniscus

Zhang

Cheriyan

Martin

et al. 2011

Journal Orthopaedic Research

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The objective of this study was to: (1) determine the distribution of lubricin in the human torn anterior cruciate ligament (ACL) and meniscus; (2) determine the distribution of lubricin in the human intact ACL and meniscus; (3) and identify potential cellular sources of lubricin in these tissues. Ten torn ACLs and six torn menisci were obtained from surgeries; for comparison, 11 intact ACLs and 13 intact menisci were obtained from total knee replacements. Samples were formalin fixed and processed for immunohistochemical staining with a monoclonal antibody for lubricin. In torn ACLs and menisci, lubricin was generally found as a discrete layer covering the torn surface. No surface lubricin staining was found on the transected edges produced during excision. Lubricin was also found on the native surfaces of intact ACLs and menisci. In all tissues, lubricin was found in the matrix and intracellularly.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Lubricin distribution in the torn human anterior cruciate ligament and meniscus

Zhang

Cheriyan

Martin

et al. 2011

Journal Orthopaedic Research

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“…TGF-b's have been shown to stimulate PRG4 production in chondrocytes, 34,[41][42][43] as well as infrapateller fat pad progenitor cells. 44 MSCs in alginate culture secrete PRG4, 19 however factors which stimulate or regulate this production are unknown.…”

Section: Discussionmentioning

confidence: 99%

Matrix molecule influence on chondrocyte phenotype and proteoglycan 4 expression by alginate‐embedded zonal chondrocytes and mesenchymal stem cells

Coates

Riggin

Fisher

2012

Journal Orthopaedic Research

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Articular cartilage resists load and provides frictionless movement at joint surfaces. The tissue is organized into the superficial, middle, deep, and calcified zones throughout its depth, each which serve distinct functions. Proteoglycan 4 (PRG4), found in the superficial zone, is a critical component of the joint's lubricating mechanisms. Maintenance of both the chondrocyte and zonal chondrocyte phenotype remain challenges for in vitro culture and tissue engineering. Here we investigate the expression of PRG4 mRNA and protein by primary bovine superficial zone chondrocytes, middle/deep zone chondrocytes, and mesenchymal stem cells encapsulated in alginate hydrogels with hyaluronic acid (HA) and chondroitin sulfate (CS) additives. Chondrogenic phenotype and differentiation markers are evaluated by mRNA expression, histochemical, and immunohistochemical staining. Results show middle/ deep cells express no measurable PRG4 mRNA by day 7. In contrast, superficial zone cells express elevated PRG4 mRNA throughout culture time. This expression can be significantly enhanced up to 15-fold by addition of both HA and CS to scaffolds. Conversely, PRG4 mRNA expression is downregulated (up to 5-fold) by CS and HA in differentiating MSCs, possibly due to build up of entrapped protein.HA and CS demonstrate favorable effects on chondrogenesis by upregulating transcription factor Sox9 mRNA (up to 4.6-fold) and downregulating type I collagen mRNA (up to 18-fold). Results highlight the important relationship between matrix components and expression of critical lubricating proteins in an engineered cartilage scaffold.

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“…While Wnt/b-catenin signaling has been found to be essential for expression of Prg4/lubricin during early development (Koyama et al 2008;Yasuhara et al 2011), the signals that maintain the expression of this locus in adult articular cartilage remain obscure. Studies have pointed to a role for both TGF-b signaling (Lee et al 2008) and mechanical loading (Nugent et al 2006a,b;Jones et al 2009) in the maintenance of Prg4/ lubricin expression in either newborn or adult articular cartilage. In this study, we both document that voluntary wheel running induces the expression of the Prg4 locus in the superficial zone of knee joint articular cartilage and identify multiple signaling pathways downstream from fluid flow shear stress (FFSS) that promote the expression of Prg4 in this tissue in a CREB-dependent manner.…”

mentioning

confidence: 99%

Mechanical motion promotes expression of Prg4 in articular cartilage via multiple CREB-dependent, fluid flow shear stress-induced signaling pathways

et al. 2014

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Lubricin is a secreted proteoglycan encoded by the Prg4 locus that is abundantly expressed by superficial zone articular chondrocytes and has been noted to both be sensitive to mechanical loading and protect against the development of osteoarthritis. In this study, we document that running induces maximal expression of Prg4 in the superficial zone of knee joint articular cartilage in a COX-2-dependent fashion, which correlates with augmented levels of phospho-S133 CREB and increased nuclear localization of CREB-regulated transcriptional coactivators (CRTCs) in this tissue. Furthermore, we found that fluid flow shear stress (FFSS) increases secretion of extracellular PGE2, PTHrP, and ATP (by epiphyseal chondrocytes), which together engage both PKA-and Ca ++ -regulated signaling pathways that work in combination to promote CREB-dependent induction of Prg4, specifically in superficial zone articular chondrocytes. Because running and FFSS both boost Prg4 expression in a COX-2-dependent fashion, our results suggest that mechanical motion may induce Prg4 expression in the superficial zone of articular cartilage by engaging the same signaling pathways activated in vitro by FFSS that promote CREB-dependent gene expression in this tissue.

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Superficial Zone Protein (Lubricin) in the Different Tissue Compartments of the Knee Joint: Modulation by Transforming Growth Factor Beta 1 and Interleukin-1 Beta

Cited by 58 publications

References 42 publications

Lubricin distribution in the torn human anterior cruciate ligament and meniscus

Lubricin distribution in the torn human anterior cruciate ligament and meniscus

Matrix molecule influence on chondrocyte phenotype and proteoglycan 4 expression by alginate‐embedded zonal chondrocytes and mesenchymal stem cells

Mechanical motion promotes expression of Prg4 in articular cartilage via multiple CREB-dependent, fluid flow shear stress-induced signaling pathways

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