Wise regulates bone deposition through genetic interactions with Lrp5.
In this study using genetic approaches in mouse we demonstrate that the secreted protein Wise plays essential roles in regulating early bone formation through its ability to modulate Wnt signaling via interactions with the Lrp5 co-receptor. In Wise-/- mutant mice we find an increase in the rate of o...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4006890?pdf=render |
| _version_ | 1818469482492854272 |
|---|---|
| author | Debra L Ellies Androulla Economou Beth Viviano Jean-Philippe Rey Stephenie Paine-Saunders Robb Krumlauf Scott Saunders |
| author_facet | Debra L Ellies Androulla Economou Beth Viviano Jean-Philippe Rey Stephenie Paine-Saunders Robb Krumlauf Scott Saunders |
| author_sort | Debra L Ellies |
| collection | DOAJ |
| description | In this study using genetic approaches in mouse we demonstrate that the secreted protein Wise plays essential roles in regulating early bone formation through its ability to modulate Wnt signaling via interactions with the Lrp5 co-receptor. In Wise-/- mutant mice we find an increase in the rate of osteoblast proliferation and a transient increase in bone mineral density. This change in proliferation is dependent upon Lrp5, as Wise;Lrp5 double mutants have normal bone mass. This suggests that Wise serves as a negative modulator of Wnt signaling in active osteoblasts. Wise and the closely related protein Sclerostin (Sost) are expressed in osteoblast cells during temporally distinct early and late phases in a manner consistent with the temporal onset of their respective increased bone density phenotypes. These data suggest that Wise and Sost may have common roles in regulating bone development through their ability to control the balance of Wnt signaling. We find that Wise is also required to potentiate proliferation in chondrocytes, serving as a potential positive modulator of Wnt activity. Our analyses demonstrate that Wise plays a key role in processes that control the number of osteoblasts and chondrocytes during bone homeostasis and provide important insight into mechanisms regulating the Wnt pathway during skeletal development. |
| first_indexed | 2024-04-13T21:25:10Z |
| format | Article |
| id | doaj.art-9ea44098e987494c916097b7f0babd09 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T21:25:10Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9ea44098e987494c916097b7f0babd092022-12-22T02:29:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9625710.1371/journal.pone.0096257Wise regulates bone deposition through genetic interactions with Lrp5.Debra L ElliesAndroulla EconomouBeth VivianoJean-Philippe ReyStephenie Paine-SaundersRobb KrumlaufScott SaundersIn this study using genetic approaches in mouse we demonstrate that the secreted protein Wise plays essential roles in regulating early bone formation through its ability to modulate Wnt signaling via interactions with the Lrp5 co-receptor. In Wise-/- mutant mice we find an increase in the rate of osteoblast proliferation and a transient increase in bone mineral density. This change in proliferation is dependent upon Lrp5, as Wise;Lrp5 double mutants have normal bone mass. This suggests that Wise serves as a negative modulator of Wnt signaling in active osteoblasts. Wise and the closely related protein Sclerostin (Sost) are expressed in osteoblast cells during temporally distinct early and late phases in a manner consistent with the temporal onset of their respective increased bone density phenotypes. These data suggest that Wise and Sost may have common roles in regulating bone development through their ability to control the balance of Wnt signaling. We find that Wise is also required to potentiate proliferation in chondrocytes, serving as a potential positive modulator of Wnt activity. Our analyses demonstrate that Wise plays a key role in processes that control the number of osteoblasts and chondrocytes during bone homeostasis and provide important insight into mechanisms regulating the Wnt pathway during skeletal development.http://europepmc.org/articles/PMC4006890?pdf=render |
| spellingShingle | Debra L Ellies Androulla Economou Beth Viviano Jean-Philippe Rey Stephenie Paine-Saunders Robb Krumlauf Scott Saunders Wise regulates bone deposition through genetic interactions with Lrp5. PLoS ONE |
| title | Wise regulates bone deposition through genetic interactions with Lrp5. |
| title_full | Wise regulates bone deposition through genetic interactions with Lrp5. |
| title_fullStr | Wise regulates bone deposition through genetic interactions with Lrp5. |
| title_full_unstemmed | Wise regulates bone deposition through genetic interactions with Lrp5. |
| title_short | Wise regulates bone deposition through genetic interactions with Lrp5. |
| title_sort | wise regulates bone deposition through genetic interactions with lrp5 |
| url | http://europepmc.org/articles/PMC4006890?pdf=render |
| work_keys_str_mv | AT debralellies wiseregulatesbonedepositionthroughgeneticinteractionswithlrp5 AT androullaeconomou wiseregulatesbonedepositionthroughgeneticinteractionswithlrp5 AT bethviviano wiseregulatesbonedepositionthroughgeneticinteractionswithlrp5 AT jeanphilipperey wiseregulatesbonedepositionthroughgeneticinteractionswithlrp5 AT stepheniepainesaunders wiseregulatesbonedepositionthroughgeneticinteractionswithlrp5 AT robbkrumlauf wiseregulatesbonedepositionthroughgeneticinteractionswithlrp5 AT scottsaunders wiseregulatesbonedepositionthroughgeneticinteractionswithlrp5 |