Syndecan-3 and the Control of Chondrocyte Proliferation during Endochondral Ossification

Shimazu, Atsushi; Nah, Hyun Duck; Kirsch, Thorsten; Koyama, Eiki; Leatherman, Judith L.; Golden, Eleanor B.; Kosher, Robert A.; Pacifici, Maurizio

doi:10.1006/excr.1996.0350

Cited by 61 publications

(50 citation statements)

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“…However, as joint formation and articular cartilage development progress, the zone of chondrocyte proliferation is relocated below the articular cap, thus becoming further away from periarticular tissues. The relocation of the proliferative zone is accompanied by an identical shift in syndecan-3 expression (Shimazu et al, 1996;Kirsch et al, 2002). Thus, it is possible that, at early stages of long bone development, chondrocyte proliferation is regulated both by PTHrP produced by periarticular tissue under Ihh influence and by Ihh itself produced by prehypertrophic chondrocytes and interacting with syndecan-3.…”

Section: Discussionmentioning

confidence: 99%

“…5B, arrowhead) which no longer occupied the epiphyseal end at this stage but was now located in the metaphysis below the articular cap ( Fig. 5B, ac; Shimazu et al, 1996;Kirsch et al, 2002). Ihh gene expression was also strong and restricted to the prehypertrophic zone (Fig.…”

Section: In Vivo Studiesmentioning

confidence: 94%

“…Cell populations rich in resting and proliferating chondrocytes isolated from the caudal and peripheral cephalic portions of day 17 chick embryo sterna (Shimazu et al, 1996) were infected with RCAS(A) viral particles encoding chick syndecan-3 and cultured for 8 to 10 days until subconfluent. Companion control cells were mock-infected and grown in parallel.…”

Section: In Vitro Analysesmentioning

confidence: 99%

“…Chondrocytes isolated from the caudal and peripheral cephalic portions of day 17 chick embryo sterna were cultured in complete medium consisting of high-glucose DMEM, 10% fetal bovine serum (FBS), 2 mM L-glutamine and 1% penicillinstreptomycin (Shimazu et al, 1996). When indicated, freshly isolated chondrocytes were infected with concentrated viral preparations, maintained for 5 to 7 days in primary culture and then subcultured into secondary cultures at 3 ϫ 10 6 cells/ 100-mm dish by trypsinization.…”

Section: Experimental Procedures Cell Cultures and Viral Infectionmentioning

confidence: 99%

“…The known four members are differentially expressed and regulate several developmental events and processes in which they act as receptors and coreceptors for factors, cytokines or matrix components such as fibronectin (Bernfield et al, 1999;Iozzo, 2001). We previously showed that syndecan-3 gene expression and distribution are restricted to the proliferative zone of the growth plate (Koyama et al, 1995;Shimazu et al, 1996;Kirsch et al, 2002), raising the possibility that syndecan-3 may participate in Ihh function in that zone and allow the factor to directly influence chondrocyte proliferation. The results presented here provide support for this possibility and are the first to identify a specific member of the syndecan family in hedgehog action.…”

Section: Introductionmentioning

confidence: 99%

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Indian hedgehog and syndecans‐3 coregulate chondrocyte proliferation and function during chick limb skeletogenesis

Shimo

Gentili

Iwamoto

et al. 2004

Developmental Dynamics

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Hedgehog proteins exert critical roles in embryogenesis and require heparan sulfate proteoglycans (HS-PGs) for action. Indian hedgehog (Ihh) is produced by prehypertrophic chondrocytes in developing long bones and regulates chondrocyte proliferation and other events, but it is not known whether it requires HS-PGs for function. Because the HS-PG syndecan-3 is preferentially expressed by proliferating chondrocytes, we tested whether it mediates Ihh action. Primary chick chondrocyte cultures were treated with recombinant Ihh (rIhh-N) in absence or presence of heparinase I or syndecan-3 neutralizing antibodies. While rIhh-N stimulated proliferation in control cultures, it failed to do so in heparinase-or antibody-treated cultures. In reciprocal gain-of-function studies, chondrocytes were made to overexpress syndecan-3 by an RCAS viral vector. Cells became more responsive to rIhh-N, but even this response was counteracted by heparinase or antibody treatment. To complement the in vitro data, RCAS viral particles were microinjected in day 4 -5 chick wing buds and effects of syndecan-3 misexpression were monitored over time. Syndecan-3 misexpression led to widespread chondrocyte proliferation and, interestingly, broader expression and distribution of Ihh. In addition, the syndecan-3 misexpressing skeletal elements were short, remained cartilaginous, lacked osteogenesis, and exhibited a markedly reduced expression of collagen X and osteopontin, products characteristic of hypertrophic chondrocytes and bone cells. The data are the first to indicate that Ihh action in chondrocyte proliferation involves syndecan-3 and to identify a specific member of the syndecan family as mediator of hedgehog function. Developmental Dynamics 229:607-617, 2004.

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Section: Discussionmentioning

confidence: 99%

Section: In Vivo Studiesmentioning

confidence: 94%

Section: In Vitro Analysesmentioning

confidence: 99%

Section: Experimental Procedures Cell Cultures and Viral Infectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Indian hedgehog and syndecans‐3 coregulate chondrocyte proliferation and function during chick limb skeletogenesis

Shimo

Gentili

Iwamoto

et al. 2004

Developmental Dynamics

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Syndecan-3 in limb skeletal development

Kosher

1998

Microsc. Res. Tech.

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Cartilage and Meniscus, Properties of

Troken¹,

Mao²,

Marion³

et al. 2006

Encyclopedia of Medical Devices and Instrumentation

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Synovial joints are created to enable movement among articulating bones. During movement, mechanical loading is transmitted across the joint, inducing mechanical stresses among all joint components such as articular cartilage, bone, meniscus, and ligaments. Articular cartilage plays critical roles in enabling motion in the synovial joint. Hyaline is the most common articular cartilage, whereas fibrocartilage is present in the semilunar meniscus of the knee, the temporomandibular joint of the jaw, and the intervertebral disk. The natural design of hyaline cartilage and fibrocartilage provides extraordinarily low friction and little wear under normal healthy conditions. However, molecular and ultrastructural structures of articular cartilage and meniscus can be destructed in diseases such as osteoarthritis and rheumatoid arthritis. For the purpose of this review, articular cartilage is discussed to represent hyaline cartilage, whereas knee meniscus is discussed as a representative of hyaline cartilage. Articular cartilage has a glassy appearance and consists of chondrocytes embedded in abundant, self‐made extracellular matrix (ECM). In contrast, knee meniscus consists of fibroblasts, chondrocytes, otherwise known as fibrochondrocytes, also embedded in self‐made ECM. Despite these superficial similarities, the composition of macromolecules in the ECM of articular cartilage and meniscus differs in important ways. Chondrocytes in articular cartilage primarily synthesize Type II collagen, whereas meniscus contains Type I and Type II collagens, likely synthesized by fibroblasts and chondrocytes separately or by fibrochondrocytes that express corresponding collagen genes. Collagen content and molecular weight in either articular cartilage or meniscus can be readily quantified. The second macromolecule in either articular cartilage or meniscus is proteoglycans. Highly negatively charged, large, and small proteoglycans retain water molecules and provide cartilage and meniscus with their resilience. From many of the studies that have formed the cornerstone of orthopedic medicine, it is known that collagen is chiefly responsible for the tensile strength of cartilage and meniscus, whereas proteoglycans provide compressive strength. Similarly, it should be recognized that collagen fibers and proteoglycan molecules cross‐anchor and function synergistically to enable walking, jogging, gymnastics, weightlifting, and innumerable physical activities human beings engage in. Rich literature exists of in‐depth characterization of articular cartilage and meniscus concerning their biology, biochemistry, and biomechanics. Observational and developmental biology studies have revealed not only the intricate compositions of articular cartilage and meniscus, but also molecular cues that regulate cellular function. For over a century, studies have explored the mechanical and physiochemical behaviors of these tissues under tension, compression, shear, hydrodynamic, and osmotic pressure loadings. Most of the sparse cells in adult articular cartilage are terminally differentiated chondrocytes engaged in matrix maintenance, rather than active chondroprogenitor cells capable of rapid proliferation. Evidently, the presence of angiogenesis favors bone formation from the same mesenchymal stem cells that, in the absence of vascularization, are capable of forming cartilage. Thus, the essential cause for the poor regenerative capacity of articular cartilage is not a lack of vascularization, but an intrinsic shortage of chondrogenic cells. Recent effort to tissue‐engineer articular cartilage and meniscus have used meritorious approaches such as stem cells or other tissue‐forming cells seeded in biocompatible porous‐permeable material scaffolds and growth factors. The novel concept of functional tissue engineering is an amalgamation of biologically based engineering approaches with physical stimulation toward the end goal of engineering a functionally adaptable articular cartilage and meniscus in vivo . This chapter will provide synthesis of the literature on biomechanical properties of articular cartilage and meniscus, and a brief update of current tissue engineering efforts to create synovial joint condyle and knee meniscus with an eventual goal toward the replacement of these diseased structures, for example, in osteoarthritis.

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Syndecan-3 and the Control of Chondrocyte Proliferation during Endochondral Ossification

Cited by 61 publications

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Indian hedgehog and syndecans‐3 coregulate chondrocyte proliferation and function during chick limb skeletogenesis

Indian hedgehog and syndecans‐3 coregulate chondrocyte proliferation and function during chick limb skeletogenesis

Syndecan-3 in limb skeletal development

Cartilage and Meniscus, Properties of

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