Bone growth in organ culture: Effects of phosphate and other nutrients on bone and cartilage

1974 ◽  
Vol 14 (1) ◽  
pp. 31-48 ◽  
Author(s):  
Patricia J. Bingham ◽  
Lawrence G. Raisz

2021 ◽  
Vol 22 (23) ◽  
pp. 12651
Author(s):  
Akari Nakamura-Utsunomiya

The accumulation of glycosaminoglycans (GAGs) in bone and cartilage leads to progressive damage in cartilage that, in turn, reduces bone growth by the destruction of the growth plate, incomplete ossification, and growth imbalance. The mechanisms of pathophysiology related to bone metabolism in mucopolysaccharidoses (MPS) include impaired chondrocyte function and the failure of endochondral ossification, which leads to the release of inflammatory cytokines via the activation of Toll-like receptors by GAGs. Although improvements in the daily living of patients with MPS have been achieved with enzyme replacement, treatment for the bone disorder is limited. There is an increasing need to identify biomarkers related to bone and cartilage to evaluate the progressive status and to monitor the treatment of MPS. Recently, new analysis methods, such as proteomic analysis, have identified new biomarkers in MPS. This review summarizes advances in clinical bone metabolism and bone biomarkers.



1979 ◽  
Vol 237 (2) ◽  
pp. E177 ◽  
Author(s):  
T O Graham ◽  
D H Van Thiel ◽  
J M Little ◽  
R Lester

Taurocholate production by fetal hepatic organ cultures was measured by radioimmunoassay. Taurocholate production was maximal on day 1 of in vitro incubation, but was demonstrable in organ cultures maintained for periods up to 15 days. Explants obtained from fetuses of 18 gestational days of age produced only 82 pmol taurocholate per milligram dry weight of tissue during the first 24 h of incubation. Explants obtained from fetuses 21 gestational days of age produced 1,043 pmol taurocholate per milligram dry weight. The presence of cortisol (2.0 X 10(-6) M) in the incubation medium increased synthesis of taurocholate by rat fetal liver in which total taurocholate rose 50-fold above control after 120 h of incubation. In increasing concentrations from 2.0 X 10(-9) M to 2.0 X 10(-7) M, cortisol produced an incremental rise in taurocholate. However, additional increases in cortisol dose failed to provide further stimulation, and taurocholate production was inhibited by cortisol concentrations of 2.0 X 10(-5) M. The results provide further validation for the technique of fetal hepatic organ culture. They demonstrate that taurocholate synthesis is increasing rapidly during the final stages of gestation and show that cortisol augments taurocholate synthesis in a dose-response pattern.



1972 ◽  
Vol 51 (5) ◽  
pp. 1492-1499 ◽  
Author(s):  
Louis A. Norton ◽  
Ronald R. Moore


1971 ◽  
Vol 133 (3) ◽  
pp. 506-519 ◽  
Author(s):  
Alfred D. Heggie

H-1 virus infection of hamsters has been shown to produce runting, microcephaly, cranial lacunae, and deformed teeth in animals inoculated during the suckling period and to cause various abnormalities, including skeletal defects, in embryos infected transplacentally. To explore the pathogenesis of these effects of viral infection on bone, the response of embryonic hamster tibiae in organ culture to inoculation with the H-1 strain of picodna virus was studied. This system made possible the direct observation of the reaction of bone to virus in a regulated environment. During a period of 7–17 days after inoculation the following observations were made: (a) H-1 virus was found to infect and replicate in bone. (b) Infected bones became more translucent, slender, and elongated than control bones. (c) Bone growth as measured by increase in wet weight was reduced in infected tibiae. (d) Infected bones showed periosteal and perichondral degeneration and diminished deposits of subperiosteal bone. It was concluded that the skeletal abnormalities which develop in embryonic and suckling hamsters after H-1 virus inoculation are the direct result of viral replication in bone, and that indirect phenomena such as those associated with chronic infection need not be postulated to explain the deformities seen in these animals.



1985 ◽  
Vol 241 (1) ◽  
pp. 207-217 ◽  
Author(s):  
Klaus Unsicker ◽  
ThomasJ. Millar ◽  
ThomasH. M�ller ◽  
Hans-D. Hofmann


1969 ◽  
Vol 4 (1) ◽  
pp. 133-137
Author(s):  
T. C. APPLETON ◽  
S. R. PELC ◽  
J. T. DINGLE ◽  
HONOR B. FELL

Earlier experiments have shown that when limb-bone rudiments from 8½-day embryonic chicks are cultivated in medium containing an indigestible sugar, the perichondrial cells become intensely vacuolated, but this vacuolation does not appear in the chondrocytes, except in the articular region. Appleton's radioautographic method for demonstrating water-soluble materials was used to study the uptake, distribution and loss of 14C-labelled sucrose in 8½ limb-bone rudiments cultivated in a chemically defined medium (BGJ5). After 48 h exposure to [14C] sucrose, both perichondrium and cartilage were heavily labelled. When such explants were either washed for 1 h in BGJ5 or cultivated for a further 24 h in non-radioactive medium, labelling was almost unaffected in the perichondrial cells but was greatly reduced in the cartilage, the cells of which were almost devoid of radioactivity. The presence in the medium of 0.08 M ‘cold’ sucrose did not alter the perichondrial grain counts in the washed explants. This finding supports the view that in the perichondrial cells sucrose is taken up non-specifically by endocytosis, arid that the intense vacuolation of the cytoplasm is due to abnormal persistence of the pinocytotic vesicles in the presence of the sugar. It is concluded that failure of the chondrocytes to take up sucrose is due, not to lack of penetration of the sugar into the cartilage, but to a weak endocytotic activity of the cells.





2004 ◽  
Vol 165 (3) ◽  
pp. 433-445 ◽  
Author(s):  
Mitsuru Horiki ◽  
Takeshi Imamura ◽  
Mina Okamoto ◽  
Makoto Hayashi ◽  
Junko Murai ◽  
...  

Biochemical experiments have shown that Smad6 and Smad ubiquitin regulatory factor 1 (Smurf1) block the signal transduction of bone morphogenetic proteins (BMPs). However, their in vivo functions are largely unknown. Here, we generated transgenic mice overexpressing Smad6 in chondrocytes. Smad6 transgenic mice showed postnatal dwarfism with osteopenia and inhibition of Smad1/5/8 phosphorylation in chondrocytes. Endochondral ossification during development in these mice was associated with almost normal chondrocyte proliferation, significantly delayed chondrocyte hypertrophy, and thin trabecular bone. The reduced population of hypertrophic chondrocytes after birth seemed to be related to impaired bone growth and formation. Organ culture of cartilage rudiments showed that chondrocyte hypertrophy induced by BMP2 was inhibited in cartilage prepared from Smad6 transgenic mice. We then generated transgenic mice overexpressing Smurf1 in chondrocytes. Abnormalities were undetectable in Smurf1 transgenic mice. Mating Smad6 and Smurf1 transgenic mice produced double-transgenic pups with more delayed endochondral ossification than Smad6 transgenic mice. These results provided evidence that Smurf1 supports Smad6 function in vivo.



1996 ◽  
Vol 80 (8) ◽  
pp. 740-744 ◽  
Author(s):  
M G Ayoubi ◽  
W J Armitage ◽  
D L Easty


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