Telomere length, telomerase activity, and expression of human telomerase reverse transcriptase mRNA in growth plate of epiphyseal articular cartilage in femoral head during normal human development and in thanatophoric dysplasia.
Telomeres are important in chromosome structure and function, protecting against their degradation. However, few studies have examined telomeres in growth plates within articular cartilage during normal development. We investigated frozen sections that were obtained from 57 reference autopsy cases (aged from 16 weeks of gestation to 91 years) and from 2 patients with thanatophoric dysplasia. In the reference cases, telomere length was significantly longer in growth plates obtained from the 10 cases that were aged from 16 weeks of gestation to 10 years than in those from 47 of the adult cases (aged 20 to 91 years). In fetal, neonatal, and child cases, telomerase activity was significantly higher in the hypertrophied zone (HZ) in growth plates than in the other 3 zones. The hTERT mRNA staining intensity (staining area) was stronger (larger) in HZ and the proliferating zone than in the calcified zone and resting zone. In thanatophoric dysplasia, telomere length and telomerase activity were short and low, respectively, compared with those of normal growth plates at an equivalent age, and expression of hTERT mRNA was negative or weakly positive in all 4 zones within growth plates. These results suggest that telomere length and telomerase activity have significant effects in the growth plates of articular cartilage, particularly at developmental ages from fetus to child. We speculate that short telomere length and low telomerase activity may be important for chondrocyte differentiation in rhizomeric shortening of the limbs in thanatophoric dysplasia.
Morita
Mitsuhiro
M
Department of Orthopaedic Surgery, National Defense Medical College, Tokorozawa, Japan.
Nakanishi
Kuniaki
K
Kawai
Toshiaki
T
Fujikawa
Kyosuke
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D002358:Cartilage, Articular / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins; D005260:Female; D005270:Femur Head / Q000502:physiology; D005333:Fetus; D006132:Growth Plate / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D019098:Telomerase / Q000096:biosynthesis* / Q000378:metabolism*; D016615:Telomere / Q000502:physiology*; D013796:Thanatophoric Dysplasia / Q000201:enzymology*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase