Vascularity of Cartilage

Kuettner, Klaus E.; Pauli, Bendicht U.

doi:10.1016/b978-0-12-319501-2.50016-9

Cited by 56 publications

(48 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Starting in the 1950s, injection methods allowed visualization by microradiography and scanning electron microscopy. Morgan (1959) and others demonstrated the complexity of branching patterns of vessels in the epiphysis and metaphysis, confirming metaphyseal arterial vessels terminate proximal to the COJ, and that vessels closest to the cartilage are an irregular and dilated sinusoidal venous network of closed loops (reviewed by Brookes, 1971;Brighton, 1978;Kuettner and Pauli, 1983). Morgan (1959) also demonstrated that a ring vessel feeds into a lattice-work plexus positioned asymmetrically over the distal half of the growth plate (hypertrophic zone cartilage), making connections to both the metaphyseal and epiphyseal circulations (Irving, 1964).…”

Section: Mpm Imaging Allows Morphological Definition Of Subperichondrmentioning

confidence: 92%

In vivo delivery of fluoresceinated dextrans to the murine growth plate: Imaging of three vascular routes by multiphoton microscopy

et al. 2005

View full text Add to dashboard Cite

Bone elongation by endochondral ossification occurs through the differentiation cascade of chondrocytes of cartilaginous growth plates. Molecules from the systemic vasculature reach the growth plate from three different directions: epiphyseal, metaphyseal, and a ring vessel and plexus associated with the perichondrium. This study is an analysis of the real-time dynamics of entrance of fluoresceinated tracers of different molecular weights into the growth plate from the systemic vasculature and tests the hypothesis that molecular weight is a key variable in the determination of both the directionality and the extent of tracer movement into the growth plate. Multiphoton microscopy was used for direct in vivo imaging of the murine proximal tibial growth plate in anesthetized 4-to 5-week-old transgenic mice with green fluorescent protein linked to the collagen II promoter. Mice were given an intracardiac injection of either fluorescein (332.3 Da) or fluoresceinated dextrans of 3, 10, 40, 70 kDa, singly or sequentially. For each tracer, directionality and rate of arrival, together with extent of movement within the growth plate, were imaged in real time. For small molecules (up to 10 kDa), vascular access from all three directions was observed and entrance was equally permissive from the metaphyseal and the epiphyseal sides. Within our detection limit (a few percent of vascular concentration), 40 kDa and larger dextrans did not enter. These results have implications both for understanding systemic and paracrine regulation of growth plate chondrocytic differentiation, as well as variables associated with effective drug delivery to growth plate chondrocytes. Key words: growth plate; vasculature; multiphoton microscopy; endochondral ossificationBone elongation in children occurs by endochondral ossification in cartilaginous growth plates at the ends of long bones. Chondrocytic differentiation in the growth plate begins with clonal expansion of stem cells, continues during cellular proliferation, and ends with cellular enlargement, followed by death and replacement by bone. The kinetics of chondrocytic activity in each stage and of the regulatory transitions between them determine the rate of bone elongation achieved. As in any cellular growth system, nutrients are required to sustain the process, and multiple endocrine and paracrine inputs regulate at each stage. For growth plate cartilage, the role of the extracellular matrix also must be considered, not only as a substantive contributor to elongation per se, but through its potential role as a communication link among chondrocytes of the growth plate, and between growth plate chondrocytes and cells of surrounding tissues such as the peri-

show abstract

Section: Mpm Imaging Allows Morphological Definition Of Subperichondrmentioning

confidence: 92%

In vivo delivery of fluoresceinated dextrans to the murine growth plate: Imaging of three vascular routes by multiphoton microscopy

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Among them, cartilage and tendon/ligaments are avascular or hypovascular as characterized by a poor and limited blood supply (Benjamin and Ralphs, 2000;Kuettner and Pauli, 1983;Young and Heath, 2000). By contrast, the adjacent mesenchyme including muscle, bone and synovium are well vascularized.…”

Section: Discussionmentioning

confidence: 99%

Anti-angiogenic action of the C-terminal domain of tenomodulin that shares homology with chondromodulin-I

Oshima

Sato

Tashiro

et al. 2004

Journal of Cell Science

View full text Add to dashboard Cite

Tenomodulin (TeM) is a type II transmembrane glycoprotein that contains a C-terminal domain with homology to the mature, secreted form of chondromodulin-I (ChM-I), a cartilage-derived angiogenesis inhibitor. TeM transcripts have been found in hypovascular tissues such as tendons and ligaments but the biological activity of TeM has not yet been fully explored. Using an adenovirus expression system, we utilized the forced expression and subsequent secretion of the human TeM C-terminal 116 amino acids (Ad-shTeM) in human umbilical vein endothelial cells (HUVECs) to assess the anti-angiogenic properties of TeM. The C-terminal 120 amino acids of the human ChM-I precursor (Ad-shChM-I) was similarly expressed in HUVECs as a comparison study. Transduction of both Ad-shTeM and Ad-shChM-I resulted in significant impairment of the tube-forming activity of HUVECs, when cultured in Matrigel. Similarly, conditioned medium from COS7 cells, transfected with plasmid DNA encoding shTeM or shChM-I, inhibited tube formation of HUVECs when compared to medium derived from either COS7 cells transfected with control vector or from non-transfected cells. Upon infection of HUVECs with Ad-shTeM or Ad-shChM-I, DNA synthesis stimulated by vascular endothelial growth factor (VEGF) was reduced to 40-50% of normal levels. Additionally, in a modified Boyden chamber assay, migration of HUVECs in response to VEGF was significantly affected following transduction of either Ad-shTeM or Ad-shChM-I and these transduced HUVECs were found to spread well on type I collagen or fibronectin, but not on vitronectin. Furthermore, the transduction of either Ad-shTeM or Ad-shChM-I in human melanoma cells resulted in suppression of tumor growth in association with decreased vessel density in vivo. Hence, we have demonstrated that, similarly to ChM-1, the C-terminal domain of TeM exhibits both anti-angiogenic and anti-tumor activities when expressed in a secreted form.

show abstract

“…Subsequently the transverse septa separating terminal chondrocytes from invading vasculature are resorbed, blood vessels invade the vacated cell lacunae, and progressive vascular invasion through columns of hypertrophic chondrocytes follows (Bettex-Galland et al, 1990;Hunziker, 1994). Matrix resorption continues after vascular invasion, leaving residual longitudinal septa which are the site of osteoblast attachment and form the core of newly formed bony trabeculae (Kuettner and Pauli, 1983). The biochemical mechanisms by which cartilage resorption is achieved and vascular invasion is initiated remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Chondrocyte apoptosis in endochondral ossification of chick sterna

Gibson

Köhler

Schaffler

1995

Developmental Dynamics

134

View full text Add to dashboard Cite

In the process of endochondral ossification, chondrocytes progress through a series of maturational changes, including division and hypertrophy, that culminate in chondrocyte loss and cartilage resorption. From an investigation of morphology, DNA fragmentation, and collagen synthesis in the developing chick sterna we have characterized chondrocytes death in this process. Light microscopy of resorbing sterna demonstrated chondrocyte condensation at the interface with the invading vasculature and electron microscopy demonstrated a range of chondrocyte morphologies, including retraction from the pericellular matrix, cytoplasmic and nuclear condensation, and vesiculation suggestive of sequential changes characteristic of apoptosis.Isolation and end-labeling of DNA from chick primary ossification centers demonstrated fragmentation to nucleosome sized units, only in primary ossification centers exhibiting active resorption, and in situ detection of DNA fragmentation showed a restriction to chondrocytes at the interface with invading blood. We conclude that terminal differentiation of chondrocytes results in death by an apoptotic process prior to resorption of the tissue and invasion by blood vessels. The extent of DNA fragmentation correlated closely with the proportion of cells displaying a condensed phenotype in contralateral primary ossification centers and peaked at an early stage of resorption, suggesting that chondrocyte apoptosis may be an initiating event in tissue resorption and vascular invasion. Comparison of DNA fragmentation with expression of the hypertrophic chondrocyte phenotype, as indicated by type X collagen synthesis, suggested that DNA fragmentation was a late event in the process of chondrocyte hypertrophy and probably corresponded with chondrocyte condensation. o 1995 Wiley-Liss, Inc.

show abstract

Vascularity of Cartilage

Cited by 56 publications

References 61 publications

In vivo delivery of fluoresceinated dextrans to the murine growth plate: Imaging of three vascular routes by multiphoton microscopy

In vivo delivery of fluoresceinated dextrans to the murine growth plate: Imaging of three vascular routes by multiphoton microscopy

Anti-angiogenic action of the C-terminal domain of tenomodulin that shares homology with chondromodulin-I

Chondrocyte apoptosis in endochondral ossification of chick sterna

Contact Info

Product

Resources

About