Different bone growth rates are associated with changes in the expression pattern of types II and X collagens and collagenase 3 in proximal growth plates of the rat tibia.
Skeletal growth depends on endochondral ossification in growth plate cartilage, where proliferation of chondrocytes, matrix synthesis, and increases in chondrocyte size all contribute to the final length of a bone. To learn more about the potential role of matrix synthesis/degradation dynamics in the determination of bone growth rate, we investigated the expression of matrix collagens and collagenase 3 in tibial growth plates in three age groups of rats (21, 35, and 80 days after birth), each characterized by specific growth rates. By combining stereological and in situ hybridization techniques, it was found that the expression of matrix collagens and collagenase 3 was specifically turned on or off at specific stages of the chondrocyte-differentiation cycle, and these changes occurred as a temporal sequence that varied depending of animal growth rate. Furthermore, the expression of these matrix proteins by a growth plate chondrocyte was found to be sped up or slowed down depending of the growth rate. In addition to expression of types II and X collagen, collagenase-3 expression was found to constitute a constant event in the series of changes in gene expression that takes place during the chondrocyte-differentiation process. Collagenase-3 expression was found to show a biphasic pattern: it was intermittently expressed at the proliferative phase and uniformly expressed at the hypertrophic stage. An intimate relationship between morphological and kinetic changes associated with chondrocyte hypertrophy and changes in the expression pattern of matrix collagens and collagenase 3 was observed. Present data prove that the matrix synthesis/degradation dynamics of the growth plate cartilage varied depending on growth rate; these results support the hypothesis that changes in matrix degradation and synthesis are a critical link in the sequence of tightly regulated events that lead to chondrocytic differentiation.
Alvarez
J
J
Department of Morphology and Cell Biology, School of Medicine, University of Oviedo, Asturias, Spain.
Balbín
M
M
Santos
F
F
Fernández
M
M
Ferrando
S
S
López
J M
JM
D000818:Animals; D001846:Bone Development; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D006132:Growth Plate / Q000201:enzymology / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism
D003094:Collagen; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C507083:Mmp13 protein, rat