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Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass.
J Biol Chem 2003; 278(3):1998-2007JB

Abstract

We have previously described osteoblast/osteocyte factor 45 (OF45), a novel bone-specific extracellular matrix protein, and demonstrated that its expression is tightly linked to mineralization and bone formation. In this report, we have cloned and characterized the mouse OF45 cDNA and genomic region. Mouse OF45 (also called MEPE) was similar to its rat orthologue in that its expression was increased during mineralization in osteoblast cultures and the protein was highly expressed within the osteocytes that are imbedded within bone. To further determine the role of OF45 in bone metabolism, we generated a targeted mouse line deficient in this protein. Ablation of OF45 resulted in increased bone mass. In fact, disruption of only a single allele of OF45 caused significantly increased bone mass. In addition, knockout mice were resistant to aging-associated trabecular bone loss. Cancellous bone histomorphometry revealed that the increased bone mass was the result of increased osteoblast number and osteoblast activity with unaltered osteoclast number and osteoclast surface in knockout animals. Consistent with the bone histomorphometric results, we also determined that OF45 knockout osteoblasts produced significantly more mineralized nodules in ex vivo cell cultures than did wild type osteoblasts. Osteoclastogenesis and bone resorption in ex vivo cultures was unaffected by OF45 mutation. We conclude that OF45 plays an inhibitory role in bone formation in mouse.

Authors+Show Affiliations

Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton, Connecticut 06340, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12421822

Citation

Gowen, Lori C., et al. "Targeted Disruption of the Osteoblast/osteocyte Factor 45 Gene (OF45) Results in Increased Bone Formation and Bone Mass." The Journal of Biological Chemistry, vol. 278, no. 3, 2003, pp. 1998-2007.
Gowen LC, Petersen DN, Mansolf AL, et al. Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. J Biol Chem. 2003;278(3):1998-2007.
Gowen, L. C., Petersen, D. N., Mansolf, A. L., Qi, H., Stock, J. L., Tkalcevic, G. T., ... Brown, T. A. (2003). Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. The Journal of Biological Chemistry, 278(3), pp. 1998-2007.
Gowen LC, et al. Targeted Disruption of the Osteoblast/osteocyte Factor 45 Gene (OF45) Results in Increased Bone Formation and Bone Mass. J Biol Chem. 2003 Jan 17;278(3):1998-2007. PubMed PMID: 12421822.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. AU - Gowen,Lori C, AU - Petersen,Donna N, AU - Mansolf,Amy L, AU - Qi,Hong, AU - Stock,Jeffrey L, AU - Tkalcevic,George T, AU - Simmons,Hollis A, AU - Crawford,David T, AU - Chidsey-Frink,Kristen L, AU - Ke,Hua Zhu, AU - McNeish,John D, AU - Brown,Thomas A, Y1 - 2002/11/05/ PY - 2002/11/8/pubmed PY - 2003/2/15/medline PY - 2002/11/8/entrez SP - 1998 EP - 2007 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 278 IS - 3 N2 - We have previously described osteoblast/osteocyte factor 45 (OF45), a novel bone-specific extracellular matrix protein, and demonstrated that its expression is tightly linked to mineralization and bone formation. In this report, we have cloned and characterized the mouse OF45 cDNA and genomic region. Mouse OF45 (also called MEPE) was similar to its rat orthologue in that its expression was increased during mineralization in osteoblast cultures and the protein was highly expressed within the osteocytes that are imbedded within bone. To further determine the role of OF45 in bone metabolism, we generated a targeted mouse line deficient in this protein. Ablation of OF45 resulted in increased bone mass. In fact, disruption of only a single allele of OF45 caused significantly increased bone mass. In addition, knockout mice were resistant to aging-associated trabecular bone loss. Cancellous bone histomorphometry revealed that the increased bone mass was the result of increased osteoblast number and osteoblast activity with unaltered osteoclast number and osteoclast surface in knockout animals. Consistent with the bone histomorphometric results, we also determined that OF45 knockout osteoblasts produced significantly more mineralized nodules in ex vivo cell cultures than did wild type osteoblasts. Osteoclastogenesis and bone resorption in ex vivo cultures was unaffected by OF45 mutation. We conclude that OF45 plays an inhibitory role in bone formation in mouse. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/12421822/Targeted_disruption_of_the_osteoblast/osteocyte_factor_45_gene__OF45__results_in_increased_bone_formation_and_bone_mass_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=12421822 DB - PRIME DP - Unbound Medicine ER -