CCN3: lactational bone booster
Abstract Mammalian reproduction requires that nursing mothers transfer large amounts of calcium to their offspring through milk. Meeting this demand requires the activation of a brain-breast-bone circuit during lactation that coordinates changes in systemic hormones, dietary calcium intake, skeletal...
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BMC
2024-12-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-024-01344-z |
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| author | Nathan Xu Kyle Yang Mengjie Wang |
| author_facet | Nathan Xu Kyle Yang Mengjie Wang |
| author_sort | Nathan Xu |
| collection | DOAJ |
| description | Abstract Mammalian reproduction requires that nursing mothers transfer large amounts of calcium to their offspring through milk. Meeting this demand requires the activation of a brain-breast-bone circuit during lactation that coordinates changes in systemic hormones, dietary calcium intake, skeletal turnover, and calcium transport into milk. Classically, increased bone resorption via increased parathyroid hormone-related protein and low estrogen levels is the main source of calcium for milk production during lactation. Over the past few decades, investigators have described many aspects of this brain-breast-bone axis during lactation, yet many unanswered questions remain. Using a comprehensive set of parabiosis coupled with in vivo µCT, bone transplant studies, cell culturing and differentiation assays, mouse genetic models, pharmacologic interventions, hepatic viral transduction, and sequencing analysis, a recent study discovered that cellular communication network factor 3 (CCN3), derived from ARHERα/Kiss1 neurons, functions as an osteogenic hormone to sustain bone formation and progeny survival during lactation. Compelling evidence has been presented to show that (1) CCN3 expression in ARHERα/Kiss1 neurons fluctuates, almost exclusively appearing during lactation; (2) CCN3 stimulates mouse and human skeletal stem cell activity, increases bone remodeling and fracture repair in young and old mice of both sexes; (3) knockdown Ccn3 transcripts in the ARHKiss1 neurons in lactating dams causes devastating bone loss and failure to sustain progeny survival. These findings suggested that the stage-specific expression of CCN3 in female ARHERα/Kiss1 neurons during lactation is a newly identified brain-bone axis evolved to sustain the skeleton in mammalian mothers and offspring. |
| format | Article |
| id | doaj-art-f2f2cb55e3c44e4d917bef781d583ce0 |
| institution | Kabale University |
| issn | 2045-3701 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | Cell & Bioscience |
| spelling | doaj-art-f2f2cb55e3c44e4d917bef781d583ce02025-01-05T12:47:53ZengBMCCell & Bioscience2045-37012024-12-011411510.1186/s13578-024-01344-zCCN3: lactational bone boosterNathan Xu0Kyle Yang1Mengjie Wang2USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of MedicineUSDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of MedicineUSDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of MedicineAbstract Mammalian reproduction requires that nursing mothers transfer large amounts of calcium to their offspring through milk. Meeting this demand requires the activation of a brain-breast-bone circuit during lactation that coordinates changes in systemic hormones, dietary calcium intake, skeletal turnover, and calcium transport into milk. Classically, increased bone resorption via increased parathyroid hormone-related protein and low estrogen levels is the main source of calcium for milk production during lactation. Over the past few decades, investigators have described many aspects of this brain-breast-bone axis during lactation, yet many unanswered questions remain. Using a comprehensive set of parabiosis coupled with in vivo µCT, bone transplant studies, cell culturing and differentiation assays, mouse genetic models, pharmacologic interventions, hepatic viral transduction, and sequencing analysis, a recent study discovered that cellular communication network factor 3 (CCN3), derived from ARHERα/Kiss1 neurons, functions as an osteogenic hormone to sustain bone formation and progeny survival during lactation. Compelling evidence has been presented to show that (1) CCN3 expression in ARHERα/Kiss1 neurons fluctuates, almost exclusively appearing during lactation; (2) CCN3 stimulates mouse and human skeletal stem cell activity, increases bone remodeling and fracture repair in young and old mice of both sexes; (3) knockdown Ccn3 transcripts in the ARHKiss1 neurons in lactating dams causes devastating bone loss and failure to sustain progeny survival. These findings suggested that the stage-specific expression of CCN3 in female ARHERα/Kiss1 neurons during lactation is a newly identified brain-bone axis evolved to sustain the skeleton in mammalian mothers and offspring.https://doi.org/10.1186/s13578-024-01344-zCCN3ARHERα/Kiss1 neuronsBone formationLactationBrain-breast-bone axis |
| spellingShingle | Nathan Xu Kyle Yang Mengjie Wang CCN3: lactational bone booster Cell & Bioscience CCN3 ARHERα/Kiss1 neurons Bone formation Lactation Brain-breast-bone axis |
| title | CCN3: lactational bone booster |
| title_full | CCN3: lactational bone booster |
| title_fullStr | CCN3: lactational bone booster |
| title_full_unstemmed | CCN3: lactational bone booster |
| title_short | CCN3: lactational bone booster |
| title_sort | ccn3 lactational bone booster |
| topic | CCN3 ARHERα/Kiss1 neurons Bone formation Lactation Brain-breast-bone axis |
| url | https://doi.org/10.1186/s13578-024-01344-z |
| work_keys_str_mv | AT nathanxu ccn3lactationalbonebooster AT kyleyang ccn3lactationalbonebooster AT mengjiewang ccn3lactationalbonebooster |