Collagen IX-deficiency seriously compromises growth cartilage development in mice.
For a large part, skeletal development, growth, and repair occur by endochondral ossification which comprises an orderly sequence of consecutive steps of proliferation and late differentiation of chondrocytes. After vascular invasion into hypertrophic cartilage, the tissue is remodelled into bone. At all stages, the process is under tight environmental control exerted by a combination of regulators, including nutritional supply and signalling through growth factors, hormones, and cell-matrix-interactions. Therefore, genetic elimination of collagen IX, a stabilizing component of the periphery of thin cartilage fibrils, is expected to compromise extracellular matrix properties and, hence, the chondrocyte environment required for normal cartilage development and homeostasis. Here, we have shown that growth plate cartilage morphology is markedly disturbed in mice lacking collagen IX. Abnormalities were most prominent in late proliferative, pre-hypertrophic, and hypertrophic zones whereas resting and early proliferative zones were less affected. In central epiphyseal regions of long bones, newborn animals show grossly abnormal areas with strongly reduced cell numbers, irregular distribution of glycosaminoglycans in the extracellular matrix, and a profoundly disturbed columnar arrangement of chondrocytes with an irregular beta1 integrin immunostaining. As a result, all long bones are shorter and broader in newborn Col9a1-/- mice. Remarkably, these abnormalities are attenuated in adult mice, but the number of cells per area still is too low due to reduced cell proliferation.
Dreier
Rita
R
Insitute for Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
Opolka
Alfred
A
Grifka
Joachim
J
Bruckner
Peter
P
Grässel
Susanne
S
D000375:Aging / Q000502:physiology; D000818:Animals; D002356:Cartilage / Q000002:abnormalities* / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D024081:Collagen Type IX / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D006132:Growth Plate / Q000166:cytology / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout
D024081:Collagen Type IX; D019012:Integrin beta1