אסיף מאגר המחקר החקלאי

CMF608 - A novel mechanical strain-induced bone-specific protein expressed in early osteochondroprogenitor cells

Year:

2004

Source of publication :

Authors :

Volume :

34

Co-Authors:

Segev, O., Quark Biotech Inc., Fremont, CA 94555, United States, Hy Laboratories Ltd., Park Tamar, Rehovot 76326, Israel
Samach, A., Quark Biotech Inc., Fremont, CA 94555, United States
Faerman, A., Quark Biotech Inc., Fremont, CA 94555, United States
Kalinski, H., Quark Biotech Inc., Fremont, CA 94555, United States
Beiman, M., Quark Biotech Inc., Fremont, CA 94555, United States
Gelfand, A., Quark Biotech Inc., Fremont, CA 94555, United States
Turam, H., Quark Biotech Inc., Fremont, CA 94555, United States
Boguslavsky, S., Quark Biotech Inc., Fremont, CA 94555, United States, Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
Moshayov, A., Quark Biotech Inc., Fremont, CA 94555, United States
Gottlieb, H., Quark Biotech Inc., Fremont, CA 94555, United States
Kazanov, E., Quark Biotech Inc., Fremont, CA 94555, United States
Nevo, Z., Department of Clinical Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel
Robinson, D., Department of Clinical Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel
Skaliter, R., Quark Biotech Inc., Fremont, CA 94555, United States
Einat, P., Quark Biotech Inc., Fremont, CA 94555, United States
Binderman, I., Department of Oral Biology, Maurice Gabriela Goldschleger S., Tel Aviv University, Tel Aviv, Israel
Feinstein, E., Quark Biotech Inc., Fremont, CA 94555, United States, Quark Biotech. Inc., QBI Enterprises, Ltd., Weizmann Science Park, PO Box 4071, Ness Ziona 70400, Israel

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Abstract:

Microarray gene expression analysis was utilized to identify genes upregulated in primary rat calvaria cultures in response to mechanical force. One of the identified genes designated CMF608 appeared to be novel. The corresponding full-length cDNA was cloned and characterized in more details. It encodes a putative 2597 amino acid protein containing N-terminal signal peptide, six leucine-rich repeats (LRRs), and 12 immunoglobulin-like repeats, 10 of which are clustered within the C-terminus. Expression of CMF608 is bone-specific and the main type of CMF608-positive cells is mesenchymal osteochondroprogenitors with fibroblast-like morphology. These cells reside in the perichondral fibrous ring of La Croix, periosteum, endosteum of normal bone as well as in the activated periosteum and early fibrous callus generated postfracture. Expression of CMF608 is notably absent from the regions of endochondral ossification. Mature bone cell types do not produce CMF608 with the exception of chondrocytes of the tangential layer of the articular cartilage, which are thought to be under constant mechanical loading. Ectopic expression of CMF608 in HEK293T cells shows that the protein is subjected to post-translational processing and its N-terminal approximately 90 kDa polypeptide can be found in the conditioned medium. Ectopic expression of either the full-length cDNA of CMF608 or of its N-terminal region in CMF608-negative ROS17/2.8 rat osteosarcoma cells results in transfected clones displaying increased proliferation rate and the characteristics of less-differentiated osteoblasts compared to the control cells. Our data indicate that CMF608 is a unique marker of early osteochondroprogenitor cells. We propose that it could be functionally involved in maintenance of the osteochondroprogenitor cells pool and its down-regulation precedes terminal differentiation. © 2003 Elsevier Inc. All rights reserved.

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