Alterations of chondroitin sulfate synthesized by chick embryo cartilage cultured in the presence of 6-aminonicotinamide

Development ◽  
1980 ◽  
Vol 59 (1) ◽  
pp. 207-216
Author(s):  
Robert E. Seegmiller ◽  
Allen L. Horwitz ◽  
Albert Dorfman
Keyword(s):  
Chondroitin Sulfate ◽  
Anaerobic Metabolism ◽  
Major Constituent ◽  
Endochondral Bone Formation ◽  
Gel Chromatography ◽  
Chick Embryos ◽  
Endochondral Bone ◽  
Cartilage Development ◽  
Integral Role

Treatment of day-4 chick embryos with 6-aminonicotinamide (6-AN) impairs limb chondrogenesis and produces micromelia. Interference with limb cartilage development may be related to decreased NAD-dependent synthesis of ATP due to the fact that chondrogenesis is dependent upon anaerobic metabolism. To better understand the effect of 6-AN on chondrogenesis, isolated cartilage epiphyses from day-11 chick embryos were treated in vitro. Sulfate incorporation into total glycosaminoglycans of treated epiphyses was 30 % of control. Incorporation of [3H]glucosamine was normal. Fractionation by gel chromatography showed that 40 % of the glycosaminoglycans synthesized by treated cells had a molecular weight of less than 15000 compared with 5 % of that of the control. A decrease in amount of chondroitin 6-sulfate, an increase of chondroitin 4-sulfate and no change in amount of unsulfated polysaccharide were observed. These results suggest that, upon exposure to 6-AN, chondrocytes produce shorter than normal chondroitin sulfate chains that are preferentially sulfated in the 4 position. Since endochondral bone formation plays an integral role in growth and development of the limb, a defect in production of chondroitin sulfate, a major constituent of cartilage matrix, appears to be involved in 6-AN-induced micromelia.

Impaired energy metabolism as an initial step in the mechanism for 6-aminonicotinamide-induced limb malformation

Development ◽  
1980 ◽  
Vol 59 (1) ◽  
pp. 217-222
Author(s):  
Yal C. Sheffield ◽  
Robert E. Seegmiller
Keyword(s):  
Amino Acid ◽  
Energy Metabolism ◽  
Chick Embryo ◽  
Chondroitin Sulfate ◽  
Atp Synthesis ◽  
Initial Step ◽  
Chick Embryos ◽  
Impaired Energy Metabolism ◽  
All Treatment

The analogue and antagonist of nicotinamide, 6-aminonicotinamide (6-AN), impairs cartilage formation and results in shortening of the limbs when administered to chick embryos. Studies have shown that 6-AN forms an abnormal NAD analogue which inhibits the activity of NAD-dependent enzymes associated with production of ATP. To determine if an effect on ATP synthesis might be associated with the mechanism of teratogenesis in the chick embryo, ATP levels of cartilage from day-8 chick embryos treated in vitro were assayed in relation to biosynthesis of protein, DNA and chondroitin sulfate. Incorporation of 35SO4− was inhibited by 6 h of treatment with 10 µg/ml of 6-AN, whereas incorporation of [3H]thymidine and [3H]amino acid was not inhibited until 12 h. Incorporation of [3H]- glucosamine was increased at all treatment times. A decrease in the level of ATP preceded any detectable inhibition of precursor incorporation. These results are consistent with the hypothesis that 6-AN inhibits chondroitin sulfate synthesis through a reduction in the level of ATP in chondrocytes.

Fetal Jaw Movement Affects Condylar Cartilage Development

2005 ◽  
Vol 84 (5) ◽  
pp. 474-479 ◽  
Author(s):  
H. Habib ◽  
T. Hatta ◽  
J. Udagawa ◽  
L. Zhang ◽  
Y. Yoshimura ◽  
...  
Keyword(s):  
Bone Formation ◽  
Mandibular Condyle ◽  
Hypertrophic Chondrocytes ◽  
Endochondral Bone Formation ◽  
Condylar Cartilage ◽  
Mechanical Factor ◽  
Endochondral Bone ◽  
Jaw Movement ◽  
Cartilage Development ◽  
Number Of Cells

Using a mouse exo utero system to examine the effects of fetal jaw movement on the development of condylar cartilage, we assessed the effects of restraint of the animals’ mouths from opening, by suture, at embryonic day (E)15.5. We hypothesized that pre-natal jaw movement is an important mechanical factor in endochondral bone formation of the mandibular condyle. Condylar cartilage was reduced in size, and the bone-cartilage margin was ill-defined in the sutured group at E18.5. Volume, total number of cells, and number of 5-bromo-2′-deoxyuridine-positive cells in the mesenchymal zone were lower in the sutured group than in the non-sutured group at E16.5 and E18.5. Hypertrophic chondrocytes were larger, whereas fewer apoptotic chondrocytes and osteoclasts were observed in the hypertrophic zone in the sutured group at E18.5. Analysis of our data revealed that restricted fetal TMJ movement influences the process of endochondral bone formation of condylar cartilage.

Effects of in vitro chondrogenic priming time of bone-marrow-derived mesenchymal stromal cells on in vivo endochondral bone formation

2015 ◽  
Vol 13 ◽  
pp. 254-265 ◽  
Author(s):  
Wanxun Yang ◽  
Sanne K. Both ◽  
Gerjo J.V.M. van Osch ◽  
Yining Wang ◽  
John A. Jansen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Endochondral Bone Formation ◽  
Endochondral Bone

scholarly journals Macromolecular organization of chicken type X collagen in vitro.

1991 ◽  
Vol 114 (3) ◽  
pp. 597-604 ◽  
Author(s):  
A P Kwan ◽  
C E Cummings ◽  
J A Chapman ◽  
M E Grant
Keyword(s):  
Self Assembly ◽  
Primary Cultures ◽  
Hexagonal Lattice ◽  
Hypertrophic Chondrocytes ◽  
Endochondral Bone Formation ◽  
Type X Collagen ◽  
Endochondral Bone ◽  
Prolonged Incubation ◽  
Carboxy Terminal

The macromolecular structure of type X collagen in the matrices of primary cultures of chick hypertrophic chondrocytes was initially investigated using immunoelectron microscopy. Type X collagen was observed to assemble into a matlike structure with-in the matrix elaborated by hypertrophic chondrocytes. The process of self assembly was investigated at the molecular level using purified chick type X collagen and rotary-shadowing EM. It was shown that under neutral conditions at 34 degrees C, individual type X collagen molecules associate rapidly into multimeric clusters via their carboxy-terminal globular domains forming structures with a central nodule of carboxy-terminal domains and the triple helices radiating outwards. Prolonged incubation resulted in the formation of a regular hexagonal lattice by lateral association of the juxtaposed triple-helical domains from adjacent multimeric clusters. This extended lattice may play an important role in modifying the cartilage matrix for subsequent events occurring in endochondral bone formation.

Identifying Candidate Mechanoregulators of Skeletal Development

2009 ◽  
Author(s):  
Niamh C. Nowlan ◽  
Patrick J. Prendergast ◽  
Shahragim Tajbakhsh ◽  
Paula Murphy
Keyword(s):  
Skeletal Muscle ◽  
Endochondral Ossification ◽  
Muscle Development ◽  
Skeletal Development ◽  
Endochondral Bone Formation ◽  
Mechanical Forces ◽  
Endochondral Bone ◽  
Mutant Strains ◽  
The Relationship

Studying the relationship between mechanical forces and skeletal development can provide vital clues to the mechanoregulation of skeletogenesis, providing important information to tissue engineers hoping to create functional cartilage or bone in vitro. Many studies of the mechanoregulation of skeletal development have focused on the chick embryo e.g., [1, 2]. However, as no endochondral ossification takes place in the embryonic chick long bones [1], mammalian systems must be used to examine the effect of mechanical forces on endochondral bone formation. Mouse mutant strains exist in which muscle development is affected, providing models with which to examine skeletogenesis in the absence of skeletal muscle contractions. One such strain is Pax3sp/sp [3], also known as splotch. The splotch mutant lacks the transcription factor Pax3, which prevents the migration of muscle pre-cursor cells into the limb buds, resulting in a complete absence of skeletal muscle.

scholarly journals Chondromodulin I Is a Bone Remodeling Factor

2003 ◽  
Vol 23 (2) ◽  
pp. 636-644 ◽  
Author(s):  
Yuko Nakamichi ◽  
Chisa Shukunami ◽  
Takashi Yamada ◽  
Ken-ichi Aihara ◽  
Hirotaka Kawano ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Remodeling ◽  
Endochondral Bone Formation ◽  
Growth Stages ◽  
Mineral Density ◽  
Targeted Disruption ◽  
Endochondral Bone ◽  
Cartilage Development ◽  
And Cartilage ◽  
Cultured Chondrocytes

ABSTRACT Chondromodulin I (ChM-I) was supposed from its limited expression in cartilage and its functions in cultured chondrocytes as a major regulator in cartilage development. Here, we generated mice deficient in ChM-I by targeted disruption of the ChM-I gene. No overt abnormality was detected in endochondral bone formation during embryogenesis and cartilage development during growth stages of ChM-I−/− mice. However, a significant increase in bone mineral density with lowered bone resorption with respect to formation was unexpectedly found in adult ChM-I−/− mice. Thus, the present study established that ChM-I is a bone remodeling factor.

scholarly journals Transglutaminase-catalyzed matrix cross-linking in differentiating cartilage: identification of osteonectin as a major glutaminyl substrate.

1995 ◽  
Vol 129 (3) ◽  
pp. 881-892 ◽  
Author(s):  
D Aeschlimann ◽  
O Kaupp ◽  
M Paulsson
Keyword(s):  
Tissue Transglutaminase ◽  
Physiological Mechanism ◽  
Cross Linking ◽  
Endochondral Bone Formation ◽  
Cross Link ◽  
Endochondral Bone ◽  
Tracheal Cartilage ◽  
Matrix Stabilization ◽  
The Matrix

The expression of tissue transglutaminase in skeletal tissues is strictly regulated and correlates with chondrocyte differentiation and cartilage calcification in endochondral bone formation and in maturation of tracheal cartilage (Aeschlimann, D., A. Wetterwald, H. Fleisch, and M. Paulsson. 1993. J. Cell Biol. 120:1461-1470). We now demonstrate the transglutaminase reaction product, the gamma-glutamyl-epsilon-lysine cross-link, in the matrix of hypertrophic cartilage using a novel cross-link specific antibody. Incorporation of the synthetic transglutaminase substrate monodansylcadaverine (amine donor) in cultured tracheal explants reveals enzyme activity in the pericellular matrix of hypertrophic chondrocytes in the central, calcifying areas of the horseshoe-shaped cartilages. One predominant glutaminyl substrate (amine acceptor) in the chondrocyte matrix is osteonectin as revealed by incorporation of the dansyl label in culture. Indeed, nonreducible osteonectin-containing complexes of approximately 65, 90, and 175 kD can be extracted from mature tracheal cartilage. In vitro cross-linking of osteonectin by tissue transglutaminase gives similar products of approximately 90 and 175 kD, indicating that the complexes in cartilage represent osteonectin oligomers. The demonstration of extracellular transglutaminase activity in differentiating cartilage, i.e., cross-linking of osteonectin in situ, shows that tissue transglutaminase-catalyzed cross-linking is a physiological mechanism for cartilage matrix stabilization.

scholarly journals In Vitro and in Vivo Endochondral Bone Formation Models Allow Identification of Anti-Angiogenic Compounds

2003 ◽  
Vol 163 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Gabri van der Pluijm ◽  
Martine Deckers ◽  
Bianca Sijmons ◽  
Henny de Groot ◽  
John Bird ◽  
...  
Keyword(s):  
Bone Formation ◽  
Endochondral Bone Formation ◽  
Endochondral Bone

Perichondrial localization of ETA receptor in rat tracheal and xiphoid cartilage and in fetal rat epiphysis

1995 ◽  
Vol 268 (2) ◽  
pp. C496-C502 ◽  
Author(s):  
K. M. Lodhi ◽  
H. Sakaguchi ◽  
S. Hirose ◽  
S. Shibabe ◽  
H. Hagiwara
Keyword(s):  
Endochondral Bone Formation ◽  
Receptor Subtype ◽  
Endothelin Receptor ◽  
Connective Tissues ◽  
Receptor System ◽  
Endochondral Bone ◽  
Fetal Rat ◽  
Eta Receptor ◽  
Subtype A

Autoradiographic studies using 125I-labeled endothelin-1 (ET-1) on sections of rat cartilage tissues, including the trachea, xiphisternum, and fetal rat epiphysis, revealed dense localization of endothelin receptors in the perichondrium. In contrast, the binding of ET-1 was not detected in the chondrocytes, cartilage matrix, and other connective tissues of the cartilage tissues tested. The perichondrial binding of 125I-ET-1 was completely abolished with BQ-123 [an endothelin receptor subtype A (ETA) antagonist] but not with BQ-3020 (an ETB agonist), and we demonstrated the perichondrial localization of ETA receptors. [3H]thymidine incorporation in vitro was significantly increased in rat xiphoid cartilage tissues exposed to ET-1. These findings suggest that the ET-1/ETA receptor system plays an important role in regulating cartilage metabolism and endochondral bone formation.

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