The authors have no conflict of interest.
Impaired Vascular Invasion of Cbfa1-Deficient Cartilage Engrafted in the Spleen†
Article first published online: 1 JUL 2002
Copyright © 2002 ASBMR
Journal of Bone and Mineral Research
Volume 17, Issue 7, pages 1297–1305, July 2002
How to Cite
Himeno, M., Enomoto, H., Liu, W., Ishizeki, K., Nomura, S., Kitamura, Y. and Komori, T. (2002), Impaired Vascular Invasion of Cbfa1-Deficient Cartilage Engrafted in the Spleen. J Bone Miner Res, 17: 1297–1305. doi: 10.1359/jbmr.2002.17.7.1297
- Issue published online: 2 DEC 2009
- Article first published online: 1 JUL 2002
- Manuscript Accepted: 6 FEB 2002
- Manuscript Revised: 14 JAN 2002
- Manuscript Received: 19 JUN 2001
- vascular invasion;
- bone marrow
Chondrocyte maturation and vascular invasion of cartilage are essential in the process of endochondral ossification. Cbfa1-deficient (Cbfa1−/−) mice displayed a complete absence of osteoblast and osteoclast maturation as well as severely inhibited chondrocyte maturation in most parts of the skeleton. Although chondrocyte maturation and mineralization were observed in restricted areas of Cbfa1−/− mouse skeleton, vascular invasion of calcified cartilage was never noted. To investigate the possibility of chondrocyte maturation and vascular invasion in Cbfa1−/− cartilage and the role of the hematopoietic system in the process of vascular invasion, we transplanted embryonic day 18.5 (E18.5) Cbfa1−/− femurs, which are composed of immature chondrocytes, into spleens of normal mice. One week later, the transplanted femurs contained terminally differentiated chondrocytes expressing osteopontin, bone sialoprotein (BSP), and matrix metalloproteinase (MMP) 13. In the diaphyses of the transplants, the cartilage matrix was mineralized and the cartilage was invaded by vascular vessels and osteoclasts. However, chondrocyte maturation and vascular invasion were severely retarded in comparison with transplants of E14.5 wild-type femurs, in which the cartilage was rapidly replaced by bone, and neither mature osteoblasts nor bone formation were observed. In primary culture of Cbfa1−/− chondrocytes, transforming growth factor (TGF) β1, platelet-derived growth factor (PDGF), interleukin (IL)-1β, and thyroid hormone (T3) induced osteopontin and MMP-13 expression. These findings indicated that factors in the hematopoietic system are able to support vascular invasion of cartilage independent of Cbfa1 but are less effective without it, suggesting that Cbfa1 functions in cooperation with factors from bone marrow in the process of growth plate vascularization.