Entry - *602383 - OSTEOGLYCIN; OGN - OMIM
 
* 602383

OSTEOGLYCIN; OGN


Alternative titles; symbols

OSTEOINDUCTIVE FACTOR; OIF
MIMECAN


HGNC Approved Gene Symbol: OGN

Cytogenetic location: 9q22.31     Genomic coordinates (GRCh38): 9:92,383,268-92,404,699 (from NCBI)


TEXT

Cloning and Expression

Using primers based on the sequence of purified bovine Oif, Madisen et al. (1990) isolated a human OGN cDNA clone by RT-PCR of osteosarcoma cell mRNA. The human gene encodes a predicted 298-amino acid precursor protein that is processed into a 103-amino acid mature protein with 96% identity to the bovine protein. Northern blot analysis detected 3 OGN mRNAs exclusively in 2 human osteosarcoma cell lines.

Hu et al. (2005) determined that mimecan is expressed in the mouse and human anterior pituitary gland.


Gene Function

Using luciferase reporter analysis and electrophoretic mobility shift assays, Hu et al. (2005) showed that PIT1 (173110) activates the human mimecan promoter through PIT1 response element sites.

Hu et al. (2005) found that, among 20 pituitary tumors, mimecan was expressed in almost all ACTH- or GH-secreting tumors and only a portion of PRL-, TSH-, or LH-positive tumors.

To dissect the major determinants of left ventricular mass, Petretto et al. (2008) combined expression quantitative trait locus and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, Petretto et al. (2008) identified osteoglycin (Ogn) as a major candidate regulator of rat left ventricular mass, with increased Ogn protein expression associated with elevated left ventricular mass. Next, Petretto et al. (2008) applied genomewide QTT analysis to the human heart and observed that, out of approximately 22,000 transcripts, OGN transcript abundance had the highest correlation with left ventricular mass. Finally, Petretto et al. (2008) confirmed a role for Ogn in the in vivo regulation of left ventricular mass in Ogn knockout mice. Taken together, Petretto et al. (2008) concluded that their data implicated Ogn as a key regulator of left ventricular mass in rats, mice, and humans, and suggested that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis.

Tanaka et al. (2012) found that Ogn expression increased during osteoblastic differentiation of both mouse MC3T3-E1 osteoblast precursors and Bmp2 (112261)-stimulated mouse C2C12 myoblasts. In C2C12 cells, Ogn expression depended upon Bmp2. Ogn expression also increased during myotube differentiation of horse serum-stimulated C2C12 cells. Overexpression of human OGN suppressed Runx2 (600211) and osterix (SP7; 606633) mRNA levels, enhanced Col1 (see 120150), Alp (ALPL; 171760), and Ocn (BGLAP; 112260) mRNA levels, and induced mineralization in MC3T3-E1 cells. In C2C12 cells, overexpression of human OGN suppressed Bmp2-induced expression of Runx2, osterix, Col1, Alp, and Ocn mRNA. Conditioned medium from OGN-overexpressing C2C12 cells decreased Runx2 and osterix mRNA levels and increased Col1, Alp, and Ocn mRNA levels in MC3T3-E1 cells and mouse primary osteoblasts. Expression of the BMP receptor ACVR1 (102576) with the arg206-to-his (R206H; 102576.0001) mutation, which constitutively activates the receptor and causes fibrodysplasia ossificans progressiva (FOP; 135100), resulted in significant downregulation of Ogn in C2C12 myoblasts. Tanaka et al. (2012) hypothesized that OGN, secreted from myoblasts, has bone anabolic activity.


Mapping

By FISH, Tasheva et al. (2000) mapped the OGN gene to chromosome 9q22. Pellegata et al. (2000) cloned the human OGN gene and mapped it to a region approximately 1.1 Mb telomeric of WI-532 and approximately 700 kb centromeric of D9S197 in 9q22.31.


REFERENCES

  1. Hu, S.-M., Li, F., Yu, H.-M., Li, R.-Y., Ma, Q.-Y., Ye, T.-J., Lu, Z.-Y., Chen, J.-L., Song, H.-D. The mimecan gene expressed in human pituitary and regulated by pituitary transcription factor-1 as a marker for diagnosing pituitary tumors. J. Clin. Endocr. Metab. 90: 6657-6664, 2005. [PubMed: 16189248, related citations] [Full Text]

  2. Madisen, L., Neubauer, M., Plowman, G., Rosen, D., Segarini, P., Dasch, J., Thompson, A., Ziman, J., Bentz, H., Purchio, A. F. Molecular cloning of a novel bone-forming compound: osteoinductive factor. DNA Cell Biol. 9: 303-309, 1990. [PubMed: 2372374, related citations] [Full Text]

  3. Pellegata, N. S., Dieguez-Lucena, J. L., Joensuu, T., Lau, S., Montgomery, K. T., Krahe, R., Kivela, T., Kucherlapati, R., Forsius, H., de la Chapelle, A. Mutations in KERA, encoding keratocan, cause cornea plana. Nature Genet. 25: 91-95, 2000. [PubMed: 10802664, related citations] [Full Text]

  4. Petretto, E., Sarwar, R., Grieve, I., Lu, H., Kumaran, M. K., Muckett, P. J., Mangion, J., Schroen, B., Benson, M., Punjabi, P. P., Prasad, S. K., Pennell, D. J., and 13 others. Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass. Nature Genet. 40: 546-552, 2008. [PubMed: 18443592, images, related citations] [Full Text]

  5. Tanaka, K., Matsumoto, E., Higashimaki, Y., Katagiri, T., Sugimoto, T., Seino, S., Kaji, H. Role of osteoglycin in the linkage between muscle and bone. J. Biol. Chem. 287: 11616-11628, 2012. [PubMed: 22351757, images, related citations] [Full Text]

  6. Tasheva, E. S., Pettenati, M., Von Kap-Her, C., Conrad, G. W. Assignment of mimecan gene (OGN) to human chromosome band 9q22 by in situ hybridization. Cytogenet. Cell Genet. 88: 326-327, 2000. [PubMed: 10828622, related citations] [Full Text]


Patricia A. Hartz - updated : 1/14/2013
Ada Hamosh - updated : 7/29/2008
John A. Phillips, III - updated : 3/19/2007
Joanna S. Amberger - updated : 3/6/2001
Ada Hamosh - updated : 4/28/2000
Creation Date:
Rebekah S. Rasooly : 2/24/1998
mgross : 01/23/2013
terry : 1/14/2013
alopez : 8/1/2008
terry : 7/29/2008
mgross : 4/16/2007
carol : 3/19/2007
alopez : 3/7/2001
terry : 3/7/2001
joanna : 3/6/2001
alopez : 5/1/2000
terry : 4/28/2000
alopez : 2/24/1998

* 602383

OSTEOGLYCIN; OGN


Alternative titles; symbols

OSTEOINDUCTIVE FACTOR; OIF
MIMECAN


HGNC Approved Gene Symbol: OGN

Cytogenetic location: 9q22.31     Genomic coordinates (GRCh38): 9:92,383,268-92,404,699 (from NCBI)


TEXT

Cloning and Expression

Using primers based on the sequence of purified bovine Oif, Madisen et al. (1990) isolated a human OGN cDNA clone by RT-PCR of osteosarcoma cell mRNA. The human gene encodes a predicted 298-amino acid precursor protein that is processed into a 103-amino acid mature protein with 96% identity to the bovine protein. Northern blot analysis detected 3 OGN mRNAs exclusively in 2 human osteosarcoma cell lines.

Hu et al. (2005) determined that mimecan is expressed in the mouse and human anterior pituitary gland.


Gene Function

Using luciferase reporter analysis and electrophoretic mobility shift assays, Hu et al. (2005) showed that PIT1 (173110) activates the human mimecan promoter through PIT1 response element sites.

Hu et al. (2005) found that, among 20 pituitary tumors, mimecan was expressed in almost all ACTH- or GH-secreting tumors and only a portion of PRL-, TSH-, or LH-positive tumors.

To dissect the major determinants of left ventricular mass, Petretto et al. (2008) combined expression quantitative trait locus and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, Petretto et al. (2008) identified osteoglycin (Ogn) as a major candidate regulator of rat left ventricular mass, with increased Ogn protein expression associated with elevated left ventricular mass. Next, Petretto et al. (2008) applied genomewide QTT analysis to the human heart and observed that, out of approximately 22,000 transcripts, OGN transcript abundance had the highest correlation with left ventricular mass. Finally, Petretto et al. (2008) confirmed a role for Ogn in the in vivo regulation of left ventricular mass in Ogn knockout mice. Taken together, Petretto et al. (2008) concluded that their data implicated Ogn as a key regulator of left ventricular mass in rats, mice, and humans, and suggested that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis.

Tanaka et al. (2012) found that Ogn expression increased during osteoblastic differentiation of both mouse MC3T3-E1 osteoblast precursors and Bmp2 (112261)-stimulated mouse C2C12 myoblasts. In C2C12 cells, Ogn expression depended upon Bmp2. Ogn expression also increased during myotube differentiation of horse serum-stimulated C2C12 cells. Overexpression of human OGN suppressed Runx2 (600211) and osterix (SP7; 606633) mRNA levels, enhanced Col1 (see 120150), Alp (ALPL; 171760), and Ocn (BGLAP; 112260) mRNA levels, and induced mineralization in MC3T3-E1 cells. In C2C12 cells, overexpression of human OGN suppressed Bmp2-induced expression of Runx2, osterix, Col1, Alp, and Ocn mRNA. Conditioned medium from OGN-overexpressing C2C12 cells decreased Runx2 and osterix mRNA levels and increased Col1, Alp, and Ocn mRNA levels in MC3T3-E1 cells and mouse primary osteoblasts. Expression of the BMP receptor ACVR1 (102576) with the arg206-to-his (R206H; 102576.0001) mutation, which constitutively activates the receptor and causes fibrodysplasia ossificans progressiva (FOP; 135100), resulted in significant downregulation of Ogn in C2C12 myoblasts. Tanaka et al. (2012) hypothesized that OGN, secreted from myoblasts, has bone anabolic activity.


Mapping

By FISH, Tasheva et al. (2000) mapped the OGN gene to chromosome 9q22. Pellegata et al. (2000) cloned the human OGN gene and mapped it to a region approximately 1.1 Mb telomeric of WI-532 and approximately 700 kb centromeric of D9S197 in 9q22.31.


REFERENCES

  1. Hu, S.-M., Li, F., Yu, H.-M., Li, R.-Y., Ma, Q.-Y., Ye, T.-J., Lu, Z.-Y., Chen, J.-L., Song, H.-D. The mimecan gene expressed in human pituitary and regulated by pituitary transcription factor-1 as a marker for diagnosing pituitary tumors. J. Clin. Endocr. Metab. 90: 6657-6664, 2005. [PubMed: 16189248] [Full Text: https://doi.org/10.1210/jc.2005-0322]

  2. Madisen, L., Neubauer, M., Plowman, G., Rosen, D., Segarini, P., Dasch, J., Thompson, A., Ziman, J., Bentz, H., Purchio, A. F. Molecular cloning of a novel bone-forming compound: osteoinductive factor. DNA Cell Biol. 9: 303-309, 1990. [PubMed: 2372374] [Full Text: https://doi.org/10.1089/dna.1990.9.303]

  3. Pellegata, N. S., Dieguez-Lucena, J. L., Joensuu, T., Lau, S., Montgomery, K. T., Krahe, R., Kivela, T., Kucherlapati, R., Forsius, H., de la Chapelle, A. Mutations in KERA, encoding keratocan, cause cornea plana. Nature Genet. 25: 91-95, 2000. [PubMed: 10802664] [Full Text: https://doi.org/10.1038/75664]

  4. Petretto, E., Sarwar, R., Grieve, I., Lu, H., Kumaran, M. K., Muckett, P. J., Mangion, J., Schroen, B., Benson, M., Punjabi, P. P., Prasad, S. K., Pennell, D. J., and 13 others. Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass. Nature Genet. 40: 546-552, 2008. [PubMed: 18443592] [Full Text: https://doi.org/10.1038/ng.134]

  5. Tanaka, K., Matsumoto, E., Higashimaki, Y., Katagiri, T., Sugimoto, T., Seino, S., Kaji, H. Role of osteoglycin in the linkage between muscle and bone. J. Biol. Chem. 287: 11616-11628, 2012. [PubMed: 22351757] [Full Text: https://doi.org/10.1074/jbc.M111.292193]

  6. Tasheva, E. S., Pettenati, M., Von Kap-Her, C., Conrad, G. W. Assignment of mimecan gene (OGN) to human chromosome band 9q22 by in situ hybridization. Cytogenet. Cell Genet. 88: 326-327, 2000. [PubMed: 10828622] [Full Text: https://doi.org/10.1159/000015521]


Contributors:
Patricia A. Hartz - updated : 1/14/2013
Ada Hamosh - updated : 7/29/2008
John A. Phillips, III - updated : 3/19/2007
Joanna S. Amberger - updated : 3/6/2001
Ada Hamosh - updated : 4/28/2000

Creation Date:
Rebekah S. Rasooly : 2/24/1998

Edit History:
mgross : 01/23/2013
terry : 1/14/2013
alopez : 8/1/2008
terry : 7/29/2008
mgross : 4/16/2007
carol : 3/19/2007
alopez : 3/7/2001
terry : 3/7/2001
joanna : 3/6/2001
alopez : 5/1/2000
terry : 4/28/2000
alopez : 2/24/1998