SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease
The study of rare human genetic disorders has often led to some of the most significant advances in biomedical research. One such example was the body of work that resulted in the identification of the Low Density Lipoprotein-Related Protein (LRP5) as a key regulator of bone mass. Point mutations we...
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Wiley
2010-01-01
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| Series: | Journal of Osteoporosis |
| Online Access: | http://dx.doi.org/10.4061/2010/460120 |
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| author | James J. Mason Bart O. Williams |
| author_facet | James J. Mason Bart O. Williams |
| author_sort | James J. Mason |
| collection | DOAJ |
| description | The study of rare human genetic disorders has often led to some of the most significant advances in biomedical research. One such example was the body of work that resulted in the identification of the Low Density Lipoprotein-Related Protein (LRP5) as a key regulator of bone mass. Point mutations were identified that encoded forms of LRP5 associated with very high bone mass (HBM). HBM patients live to a normal age and do not appear to have increased susceptibility to carcinogenesis or other disease. Thus, devising methods to mimic the molecular consequences of this mutation to treat bone diseases associated with low bone mass is a promising avenue to pursue. Two groups of agents related to putative LRP5/6 functions are under development. One group, the focus of this paper, is based on antagonizing the functions of putative inhibitors of Wnt signaling, Dickkopf-1 (DKK1), and Sclerostin (SOST). Another group of reagents under development is based on the observation that LRP5 may function to control bone mass by regulating the secretion of serotonin from the enterrochromaffin cells of the duodenum. |
| format | Article |
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| institution | Kabale University |
| issn | 2042-0064 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Osteoporosis |
| spelling | doaj-art-0dd6ed6177a944f1a0bd82cab3b739d22025-02-03T01:32:12ZengWileyJournal of Osteoporosis2042-00642010-01-01201010.4061/2010/460120460120SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone DiseaseJames J. Mason0Bart O. Williams1Center for Skeletal Disease Research, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USACenter for Skeletal Disease Research, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USAThe study of rare human genetic disorders has often led to some of the most significant advances in biomedical research. One such example was the body of work that resulted in the identification of the Low Density Lipoprotein-Related Protein (LRP5) as a key regulator of bone mass. Point mutations were identified that encoded forms of LRP5 associated with very high bone mass (HBM). HBM patients live to a normal age and do not appear to have increased susceptibility to carcinogenesis or other disease. Thus, devising methods to mimic the molecular consequences of this mutation to treat bone diseases associated with low bone mass is a promising avenue to pursue. Two groups of agents related to putative LRP5/6 functions are under development. One group, the focus of this paper, is based on antagonizing the functions of putative inhibitors of Wnt signaling, Dickkopf-1 (DKK1), and Sclerostin (SOST). Another group of reagents under development is based on the observation that LRP5 may function to control bone mass by regulating the secretion of serotonin from the enterrochromaffin cells of the duodenum.http://dx.doi.org/10.4061/2010/460120 |
| spellingShingle | James J. Mason Bart O. Williams SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease Journal of Osteoporosis |
| title | SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease |
| title_full | SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease |
| title_fullStr | SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease |
| title_full_unstemmed | SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease |
| title_short | SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease |
| title_sort | sost and dkk antagonists of lrp family signaling as targets for treating bone disease |
| url | http://dx.doi.org/10.4061/2010/460120 |
| work_keys_str_mv | AT jamesjmason sostanddkkantagonistsoflrpfamilysignalingastargetsfortreatingbonedisease AT bartowilliams sostanddkkantagonistsoflrpfamilysignalingastargetsfortreatingbonedisease |