Expression of clusterin in the superficial zone of bovine articular cartilage

Khan, Ilyas; Salter, Donald; Bayliss, Michael T.; Thomson, B.M.; Archer, Charles W.

doi:10.1002/1529-0131(200108)44:8<1795::aid-art316>3.0.co;2-k

Cited by 31 publications

(22 citation statements)

References 12 publications

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“…Alpha-2-macroglobulin is an endoproteinase inhibitor present in blood and joint fluid which functions as a substrate for matrix enzymes such as ADAMTS-4 and -5 and inhibits their activity [44]. Clusterin is known to be a multifunctional, secreted glycoprotein expressed in diverse locations, implicated in regulating complement activation and cell death in injured and degenerating tissues, and may have a cytoprotective effect on chondrocytes including NP cells [45,46]. Tenascin is an extracellular matrix glycoprotein known to be abundant in the annulus of young IVDs and localized pericellularly in degenerated IVDs, and possibly could have a role in fibronectin - disc cell interactions [47].…”

Section: Discussionmentioning

confidence: 99%

Notochordal conditioned media from tissue increases proteoglycan accumulation and promotes a healthy nucleus pulposus phenotype in human mesenchymal stem cells

et al. 2011

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IntroductionNotochordal cells (NCs) are influential in development of the intervertebral disc (IVD) and species that retain NCs do not degenerate. IVD repair using bone marrow derived mesenchymal stem cells (MSCs) is an attractive approach and the harsh microenvironment of the IVD suggests pre-differentiation is a necessary first step. The goal of this study was to use soluble factors from NCs in alginate and NCs in their native tissue to differentiate human MSCs to a young nucleus pulposus (NP) phenotype.MethodsHuman MSCs (cultured under micromass conditions for 21 days in hypoxia) were differentiated with conditioned medium derived from porcine notochordal cells in native tissue (NCT) or in alginate beads (NCA), and compared with chondrogenic (TGFβ-3) or basal medium. A PCR array of 42 genes was utilized to screen a large number of genes known to be associated with the healthy NP phenotype and pellet cultures were also evaluated for glycosaminoglycan content, histology and viability. Proteomic analysis was used to assess candidate soluble factors in NCA and NCT.ResultsNotochordal cell conditioned media had diverse effects on MSC phenotype. NCT resulted in the highest levels of glycosaminoglycan (GAG), as well as up-regulation of SOX9 and Collagen II gene expression. NCA demonstrated effects that were catabolic yet also anti-fibrotic and minimally hypertrophic with down-regulation of Collagens I and III and low levels of Collagen X, respectively. Micromass culture and hypoxic conditions were sufficient to promote chondrogenesis demonstrating that both basal and chondrogenic media produced similar phenotypes. Candidate matricellular proteins, clusterin and tenascin were identified by proteomics in the NCA group.ConclusionsNCs secreted important soluble factors capable of differentiating MSCs to a NP phenotype synthesizing high levels of proteoglycan while also resisting collagen fiber expression and hypertrophy, yet results were sensitive to the conditions in which media was generated (cells in alginate versus cells in their native tissue) so that further mechanistic studies optimizing culture conditions and defining important NC secreted factors are required. Matricellular proteins, such as clusterin and tenascin, are likely to be important to optimize differentiation of MSCs for maximum GAG production and reduced collagen fiber expression.

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Section: Discussionmentioning

confidence: 99%

Notochordal conditioned media from tissue increases proteoglycan accumulation and promotes a healthy nucleus pulposus phenotype in human mesenchymal stem cells

et al. 2011

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“…Studies that were undertaken to further clarify the unique role of the superficial zone thus far have concentrated on cell shape (Hunziker et al, 2002;Jadin et al, 2005), cell density (Bywaters, 1937;Hunziker et al, 2002;Jadin et al, 2005;Quinn et al, 2005;Stockwell, 1971), cytoskeletal organization (Kim and Spector, 2000), growth-related changes in the bovine chondrocyte organization (Jadin et al, 2007), single cell mechanical properties (Jurvelin et al, 1996), gene expression (Darling et al, 2004;Jay et al, 2001;Khan et al, 2001;Schumacher et al, 1994), and metabolism (Eger et al, 2002). While it is widely accepted that the organization of human chondrocytes of the radial zones occur in vertical columns and the transitional zone in small "random" groups (Aydelotte and Kuettner, 1988;Brighton et al, 1984;Kuettner et al, 1991), it remains unclear how the human chondrocytes of the superficial zone are organized.…”

Section: Introductionmentioning

confidence: 99%

Distinct horizontal patterns in the spatial organization of superficial zone chondrocytes of human joints

Rolauffs

Williams

Grodzinsky

et al. 2008

Journal of Structural Biology

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A better understanding of the unique cellular and functional properties of the superficial zone of articular cartilage may aid current strategies in tissue engineering which attempts a layered design for the repair of cartilage lesions to avert or postpone the onset of osteoarthritis. However, data pertaining to the cellular organization of non-degenerated superficial zone of articular cartilage is not available for most human joints. The present study analyzed the arrangement of chondrocytes of non-degenerated human joints (shoulder, elbow, knee, and ankle) by using fluorescence microscopy of the superficial zone in a top-down view. The resulting horizontal chondrocyte arrangements were tested for randomness, homogeneity or a significant grouping via point pattern analysis and were correlated with the joint type in which they occurred. The present study demonstrated that human superficial chondrocytes occurred in four distinct patterns of strings, clusters, pairs or single chondrocytes. Those patterns represented a significant grouping (p<0.0001) with horizontal alignment. Each articular joint surface was dominated by only one of these four patterns (p<0.001). Specific patterns correlated with specific diarthrodial joint types (p<0.001). Further studies need to establish whether these organizational patterns are a consequence of their surrounding environment or whether they are linked to a functional purpose.

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“…Its mRNA and protein are reported at elevated levels in diseased tissue, and in healthy tissue it is thought to play a role in a plethora of important biological functions. Gene expression for clusterin has localized it to the superficial zone only, 50,93 identifying it as a marker for that zone. Del1 is thought to play a role in vascularization regulation and restricts endothelial cells during early development.…”

Section: Explant Culturementioning

confidence: 99%

Phenotypic Variations in Chondrocyte Subpopulations and Their Response to In Vitro Culture and External Stimuli

Coates

Fisher

2010

Ann Biomed Eng

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Articular cartilage defects have limited capacity to self-repair, and cost society up to 60 billion dollars annually in both medical treatments and loss of working days. Recent developments in cartilage tissue engineering have resulted in many new products coming to market or entering clinical trials. However, there is a distinct lack of treatments which aim to recreate the complex zonal organization of articular cartilage. Cartilage tissue withstands repetitive strains throughout an individual's lifetime and provides frictionless movement between joints. The structure and composition of its intricately organized extracellular matrix varies with tissue depth to provide optimal resistance to loading, ensure ease of movement, and integrate with the subchondral bone. Each tissue zone is specially designed to resist the load it experiences, and maximize the tissue properties needed for its location. It is unlikely that a homogenous solution to tissue repair will be able to optimally restore the function of such a heterogeneous tissue. For zonal engineering of articular cartilage to become practical, maintenance of phenotypically stable zonal cell populations must be achieved. The chondrocyte phenotype varies considerably by zone, and it is the activity of these cells that help achieve the structural organization of the tissue. This review provides an examination of literature which has studied variations in cellular phenotype between cartilage zones. By doing so, we have identified critical differences between cell populations and highlighted areas of research which show potential in the field. Current research has made the morphological and metabolic variations between these cell populations clear, but an ideal way of maintaining these differences in vitro culture is yet to be established. Combinations of delivered growth factors, mechanical loading, and layered three-dimensional culture systems all show potential for achieving this goal. Furthermore, differentiation of progenitor cell populations into chondrocyte subpopulations may also hold promise for achieving large numbers of zonal chondrocytes. Success of the field lies in establishing methods of retaining phenotypically stable cell populations for in vitro culture.

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Expression of clusterin in the superficial zone of bovine articular cartilage

Cited by 31 publications

References 12 publications

Notochordal conditioned media from tissue increases proteoglycan accumulation and promotes a healthy nucleus pulposus phenotype in human mesenchymal stem cells

Notochordal conditioned media from tissue increases proteoglycan accumulation and promotes a healthy nucleus pulposus phenotype in human mesenchymal stem cells

Distinct horizontal patterns in the spatial organization of superficial zone chondrocytes of human joints

Phenotypic Variations in Chondrocyte Subpopulations and Their Response to In Vitro Culture and External Stimuli

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