Growth plate

Epothilones are a class of molecules that show anticancer activity. Production of a synthetic intermediate was investigated through the action of an esterase on various sterically hindered 3-hydroxy esters [76]. No initial activity was observed, so a Pseudomonasfluorescens esterase was transformed into a mutator strain Epicurian coli and screened using an indicator in the growth plates that would produce a red color if hydrolysis occurred. An ee of 25% was achieved from a variant containing two mutations. 

From recent reports of the mouse model smdies, type X collagen might have an important role not only in growth plate but also in bone marrow fiinctions. " ... 

Figure 1-6-6 shows how libraries are screened to identify a desired DNA sequence. The top circle represents either a genomic library or an expression library on a growth plate. 

Agar growth plate with bacterial colonies... 

Cloning procedure (in bacteria) Recombinant plasmids transfected into bacteria Antibiotic resistance used to select bacteria with recombinant plasmids Blot growth plate and probe with P-DNA for gene, or with Tantibody for protein... 

The mechanism of G a disease may resnlt from insnfficient parathyroid hormone-related peptide signaling by the parathyroid hormone receptor 1 (PTHRl) in chondrocytes. This deficiency may inhibit the differentiation of chondrocytes within the endochondral growth plate (88,89). A variety of parathyroid hormone abnormalities can result. 

Bastepe, M., Weinstein, L. S., Ogata, N., et al. (2004) Stimulatory G protein directly regulates hypertrophic differentiation of growth plate cartilage in vivo. Proc. Natl. Acad. Sci. U. S. A. 101, 14794-14799. 

Sakamoto, A., Chen, M., Kobayashi, T., Kronenberg, H. M., and Weinstein, L. S. (2005) Chondrocyte-specific knockout of the G protein G(s)alpha leads to epiphyseal and growth plate abnormalities and ectopic chondrocyte formation. J. Bone Miner. Res. 20, 663-671. 

Epiphysial growth plate expansion is not only the pharmacologic phenotype of BMS-275291 activity, but has also been reported as the sole phenotype of mice treated with... 

Fig. 5. Rat epiphysial growth rate (on-treatment). BMS-275291 treatment of young rats induction of epiphysial growth plate expansion and suppressed blood vessel invasion in the femur of a rat given oral BMS-275291, 4000 mg/kg/d for 1 mo. This pharmacologic phenotype resembles reported phenotypes for mice with homozygous MMP-9 deletion as well as mice treated with inhibitors of VEGF signaling.

Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, et al. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 1998 93 411-422. 

Larsson, S. E. The metabolic heterogeneity of glycosaminoglycans of the different zones of the epiphyseal growth plate and the effect of ethane-l-hydroxy-l,l-diphosphonate (EHDP) upon glycosaminoglycan synthesis in vivo. Calc. Tiss. Res. 21, 67 (1976)... 

Brighton, C. T., Hunt, R. M. Mitochondrial calcium and its role in calcification. Histo-chemical localization of calcium in electron micrographs of the epiphyseal growth plate with K-pyroantimonate. Clin. Orthop. 100, 406 (1974)... 

Howell, D. S., Pita, J. C. Calcification of growth plate cartilage with special reference to studieson micropuncture fluids. Clin. Orthop. 118, 208 (1976)... 

Wang, W., and T. Kirsch, 2002, Retinoic acid stimulates annexin-mediated growth plate chondrocyte... 

Wu, L.N., Genge, B.R., Sauer, G.R., and R.E. Wuthier, 1996, Characterization and reconstitution of the nucleational complex responsible for mineral formation by growth plate cartilage matrix vesicles. Connect Tissue Res. 35(1 1) 309-15. 

Wu, S, Palese, T, Mishra, OP, Delivoria-Papadopoulos, M and De Luca, F, 2004, Effects ofCa2+ sensing receptor activation in the growth plate, Faseb J 18 143-145 Yamaguchi, T, Ye, C, Chattopadhyay, N, Sanders, JL, Vassilev, PM and Brown, EM, 2000, Enhanced expression of extracellular calcium sensing receptor in monocyte-differentiated versus undifferentiated... 

Figure 11.1 Schematic showing long bone with higher power views of the epiphyseal growth plate and cortical bone.

Figure 11.3 Studies in mutant mice, (a) Image of mineral to matrix in the growth plate of a young mouse lacking matrix gla protein (MGP—/—) and its wildtype control (MGP+/+). Note the gradient of mineral matrix ratios in the wildtype is not apparent in the knockout, (b) Mineral matrix increases at three sites in the cortices of the osteocalcin knockout (KO) mouse (6 month data), while crystallinity is decreased relative to wildtype (WT) controls, (c) In the osteonectin knockout mouse (4 months old) the collagen maturity assessed in terms of the 1660 1690 peak area ratio is increased on the periosteal and endosteal surface.

Mizoguchi I, Nakamura M, Takahashi I, Kagayama M and Mitani H (1990) An immunohistochemical study of localization of type I and type II collagens in mandibular condylar cartilage compared with tibial growth plate. Histochemistry 93 593-599. 

Thirty-seven weeks after ovariectomy, marked decreases of 73% (p <. 01) and 77% (p <. 01) in trabecular bone volume and trabecular bone number (data not shown), respectively, were observed at 1 to 5 mm of the growth plate metaphyseal junction of the proximal tibia. Simultaneously, a marked increase in trabecular bone separation from a control value in intact rats of 262 19 to 1486 236 pm (p <. 01) was observed in OVX animals. Treatment with 1 mg/kg of EM-800 and raloxifene resulted in 68% (p<. 01) and 64% (p <. 01) reversals, respectively, of the decrease in trabecular bone volume caused by ovariectomy. In fact, treatment with EM-800 and raloxifene at the daily 1 mg/kg dose increased trabecular bone volume of the proximal tibia from a control value of 5.8 0.9% in OVX animals to 16.4 0.4% and 15.8 1.0%, respectively. These stimulatory effects are not statistically different from the 53% reversal achieved with E2. At the lowest dose used (0.01 mg/kg), EM-800 already reversed by 34% (p <. 01) the elfect of OVX whereas raloxifene had no detectable effect. The administration of 0.1 mg/kg of EM-800 and raloxifene, on the other hand, resulted in 40% (p <. 01) and 24% (p <. 05) reversals, respectively, of the decrease in trabecular bone volume caused by OVX. 

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