Eva Balint and Amjad Javed have contributed equally to this work.
Runx1/AML1 hematopoietic transcription factor contributes to skeletal development in vivo†
Version of Record online: 12 MAY 2003
Copyright © 2003 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 196, Issue 2, pages 301–311, August 2003
How to Cite
Lian, J. B., Balint, E., Javed, A., Drissi, H., Vitti, R., Quinlan, E. J., Zhang, L., van Wijnen, A. J., Stein, J. L., Speck, N. and Stein, G. S. (2003), Runx1/AML1 hematopoietic transcription factor contributes to skeletal development in vivo. J. Cell. Physiol., 196: 301–311. doi: 10.1002/jcp.10316
- Issue online: 10 JUN 2003
- Version of Record online: 12 MAY 2003
- Manuscript Accepted: 18 FEB 2003
- Manuscript Received: 6 FEB 2003
- NIH. Grant Numbers: AR39588, CA82834
The requirement of Runx2 (Cbfal/AML3), a runt homology domain transcription factor essential for bone formation and osteoblast differentiation, is well established. Although Runx2 is expressed in the developing embryo prior to ossification, yet in the absence of Runx2 initial formation of the skeleton is normal, suggesting a potential redundancy in function of Runx family members. Here we addressed expression of the hematopoietic family member Runx1 (AML1/Cbfa2) in relation to skeletal development using a LacZ knock-in mouse model (Runx1lz/+). The resulting fusion protein reflects Runx1 promoter activity in its native context. Our studies show that Runx1 is expressed by prechondrocytic tissue forming the cartilaginous anlagen in the embryo, resting zone chondrocytes, suture lines of the calvarium, and in periosteal and perichondral membranes of all bone. Runx1 continues to be expressed in these tissues in adult mice, but is absent in mature cartilage or mineralized bone. However, hyaline cartilage outside the bone environment (trachea, xiphoid tissues), and epithelium of many soft tissues (trachea, thyroid, lung, skin) also express Runx1. The robust expression of Runx1 in vivo in chondroblasts at sites of cartilage growth and in osteoblasts at sites of new bone formation, suggests that Runx1 expression may be related to osteochondroprogenitor cell differentiation. This observation is further supported by high expression of Runx1 in ex vivo cultures of marrow stromal cells and calvarial derived osteoblasts from Runx1lz/+ mice. These data indicate that Runx1 may contribute to the early stages of skeletogenesis and continues to function in the progenitor cells of tissues that support bone formation in the adult. J. Cell. Physiol. 196: 301–311, 2003. © 2003 Wiley-Liss, Inc.