Chondrogenic potential of skeletal cell populations: Selective growth of chondrocytes and their morphogenesis and development in vitro

Gerstenfeld, Louis C.; Toma, Cyril D.; Schaffer, Jonathan; Landis, William J.

doi:10.1002/(sici)1097-0029(19981015)43:2<156::aid-jemt8>3.0.co;2-w

Cited by 9 publications

(7 citation statements)

References 62 publications

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“…23,29 The culture medium should include selected serum batches, and mixtures of growth factors and dexamethasone. [40][41][42][43][44][45][46][47] At least for equine MSCs, few culture techniques or growth factor additives can drive these cells to become fully differentiated chondrocytes. 38,48 Given the results of this study, using MSCs harvested from bone marrow, selected by gradient centrifugation, and induced down the chondrocytic pathway by defined medium, other mechanisms for enhanced chondrogenesis need to be established.…”

Section: Discussionmentioning

confidence: 99%

Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model

Wilke

Nydam

Nixon

2007

Journal Orthopaedic Research

269

225

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Mesenchymal stem cells (MSCs) provide an important source of pluripotent cells for musculoskeletal tissue repair. This study examined the impact of MSC implantation on cartilage healing characteristics in a large animal model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by injection of a selfpolymerizing autogenous fibrin vehicle containing mesenchymal stem cells, or autogenous fibrin alone in control joints. Arthroscopic second look and defect biopsy was obtained at 30 days, and all animals were euthanized 8 months after repair. Cartilage repair tissue and surrounding cartilage were assessed by histology, histochemistry, collagen type I and type II immunohistochemistry, collagen type II in situ hybridization, and matrix biochemical assays. Arthroscopic scores for MSCimplanted defects were significantly improved at the 30-day arthroscopic assessment. Biopsy showed MSC-implanted defects contained increased fibrous tissue with several defects containing predominantly type II collagen. Long-term assessment revealed repair tissue filled grafted and control lesions at 8 months, with no significant difference between stem cell-treated and control defects. Collagen type II and proteoglycan content in MSC-implanted and control defects were similar. Mesenchymal stem cell grafts improved the early healing response, but did not significantly enhance the long-term histologic appearance or biochemical composition of fullthickness cartilage lesions. ß

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Section: Discussionmentioning

confidence: 99%

Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model

Wilke

Nydam

Nixon

2007

Journal Orthopaedic Research

269

225

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“…This possibility is one explanation for the mild osteogenic induction stimulated by Adv‐hBMP13‐transduced cells at 3 weeks. Because ALP activity and calcium mineral accumulation are known as markers of both hypertrophic calcifying chondrocytes and osteoblasts, (36,43) type X collagen gene expression is the best denominator of the hypertrophic chondrocytes, indicating terminal differentiation of chondrocytes in chondrogenesis. Consequently, our results indicate that hBMP‐2 remarkably stimulates terminal differentiation supporting endochondral ossification, whereas hBMP‐13 stimulates chondrocyte development but not terminal differentiation (absence of hypertrophy and type X collagen) and does not support endochondral ossification.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus Mediated BMP-13 Gene Transfer Induces Chondrogenic Differentiation of Murine Mesenchymal Progenitor Cells

Nochi

Sung

Lou

et al. 2004

Journal of Bone and Mineral Research

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Chondrogenic/osteogenic differentiation of a mesenchymal progenitor stimulated by BMP-13 (CDMP-2) was studied. C3H10T1/2 cells were transduced by an adenoviral construct containing BMP-13 or BMP-2. BMP-13 supported chondrogenesis but not terminal differentiation, whereas BMP-2 stimulated endochondral ossification. The studies show that BMP-13 may fail to support terminal chondrocyte differentiation.Introduction: Bone morphogenetic protein (BMP)-13 is a member of the transforming growth factor ␤ (TGF-␤) superfamily of growth factors. Although the biological functions of BMP-13 remain poorly understood, continued postnatal expression of BMP-13 in articular cartilage suggests that this protein may function in an autocrine/paracrine fashion to regulate growth and maintenance of articular cartilage. The purpose of this study was to elucidate the role of BMP-13 in chondrogenic differentiation. Materials and Methods: Replication-deficient adenoviruses carrying human BMP-13 (Adv-hBMP13), bacterial ␤-galactosidase (Adv-␤gal), and human BMP-2 (Adv-hBMP2) were constructed. Murine mesenchymal progenitor cells (C3H10T1/2) were transduced with these vectors, and differentiation to the chondrogenic lineage was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), biochemical, and histological analyses. Results and Conclusions: Our findings revealed that hBMP-13 transduced cells differentiated into round cells that stained with Alcian blue. Analysis of gene expression in hBMP-13-transduced cells demonstrated presence of cartilage-specific markers, absence of hypertrophic chondrocyte specific markers, and upregulation of proteoglycan biosynthesis. In particular, hBMP-13-transduced cells had significantly less and delayed expression of alkaline phosphatase activity and calcium mineral accumulation than hBMP-2-transduced cells. Except for BMPR-IB/ ALK-6, expression of BMP receptors was identified constitutively in C3H10T1/2 cells and was not affected by the presence of either of the BMPs. In summary, hBMP-13, while stimulating chondrogenesis, failed to support differentiation to hypertrophic chondrocytes and endochondral ossification similar to hBMP-2. Thus, this may prove to be a useful strategy for cell-based regeneration of articular cartilage.

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“…All collected mouse sesamoid data were analyzed to document cellular and extracellular ultrastructure and the presence of matrix vesicles and collagen in the tissues. Data were compared to previously reported structure, composition, and mineralization in calcifying cartilage (Ali et al, 1970; Hsu and Anderson, 1978; Plate et al, 1996; Kirsch et al, 1997; Gerstenfeld et al, 1998), avian tendons (Landis, 1986; Landis and Song, 1991; Landis et al, 1993; Siperko and Landis, 2001; Landis and Silver, 2002), and fibrocartilage (Cooper and Misol, 1970; Yamada, 1976; Benjamin et al, 1986; Rufai et al, 1996).…”

Section: Methodsmentioning

confidence: 99%

“…A critical, yet unanswered question in this context concerns identification of the precise extracellular matrix component(s) that may be responsible for the initial deposition of mineral in these tissues. Several studies in biomineralization suggest that extracellular matrix vesicles are the first structures to initiate mineral formation in the organic matrix of calcifying cartilage (Anderson, 1969; Bonucci, 1969; Ali et al, 1970; Hsu and Anderson, 1978; Plate et al, 1996; Kirsch et al, 1997; Gerstenfeld et al, 1998), fibrocartilage (Yamada, 1976), primary dentin (Stratmann et al, 1997), fish scales (Lowenstam and Weiner, 1989), antler (Szuwart et al, 1998), and other vertebrate mineralizing tissues. Numerous additional reports provide support for collagen molecules as templates for mineral deposition in bone, dentin, cementum, and calcifying avian tendons (Bernard and Pease, 1969; Birkedal‐Hansen et al, 1977; Glimcher, 1987, 1989; Arsenault, 1989; Landis and Song, 1991; Landis et al, 1993, 1996; Siperko and Landis, 2001; Landis and Silver, 2002).…”

Section: Introductionmentioning

confidence: 99%

Murine Metapodophalangeal Sesamoid Bones: Morphology and Potential Means of Mineralization Underlying Function

Doherty

Lowder

Jacquet

et al. 2010

The Anatomical Record

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Normal murine metapodophalangeal sesamoid bones, closely associated with tendons, were examined in terms of their structure and mineralization with reference to their potential function following crystal deposition. This study utilized radiography, whole mount staining, histology and conventional electron microscopy to establish a maturation timeline of mineral formation in one- to six-week-old metapodophalangeal sesamoids from CD-1 mice. An intimate cellular and structural relationship was documented in more detail than previously described between the sesamoid bone, tendon, and fibrocartilage enthesis at the metapodophalangeal joint. Sesamoid calcification began in one-week lateral sesamoids of the murine metacarpophalangeal joint of the second digit. All sesamoids were completely calcified by four weeks. Transmission electron microscopy of two-week metacarpophalangeal sesamoids revealed extensive type I collagen in the associated tendon and fibrocartilage insertion sites and type II collagen and proteoglycan networks in the interior of the sesamoid. No extracellular matrix vesicles were documented. The results demonstrate that murine sesamoid bones consist of cartilage elaborated by chondrocytes that predominantly synthesize and secrete type II collagen and proteoglycan. Type II collagen and proteoglycans appear responsible for the onset and progression of mineral formation in this tissue. These data contribute to new understanding of the biochemistry, ultrastructure and mineralization of sesamoids in relation to other bones and calcifying cartilage and tendon of vertebrates. They also reflect on the potentially important but currently uncertain function of sesamoids as serving as a fulcrum point along a tendon, foreshortening its length and altering advantageously its biomechanical properties with respect to tendon-muscle interaction.

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Chondrogenic potential of skeletal cell populations: Selective growth of chondrocytes and their morphogenesis and development in vitro

Cited by 9 publications

References 62 publications

Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model

Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model

Adenovirus Mediated BMP-13 Gene Transfer Induces Chondrogenic Differentiation of Murine Mesenchymal Progenitor Cells

Murine Metapodophalangeal Sesamoid Bones: Morphology and Potential Means of Mineralization Underlying Function

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