Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice
The link between obesity and low bone strength has become a significant medical concern. The canonical Wnt signaling pathway is a key regulator of mesenchymal stem cell differentiation into either osteoblasts or adipocytes with active Wnt signaling promoting osteoblastogenesis. Our previous research...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Bioscientifica
2023-10-01
|
| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/12/11/EC-23-0251.xml |
| _version_ | 1797666438947799040 |
|---|---|
| author | Souad Daamouch Sylvia Thiele Lorenz Hofbauer Martina Rauner |
| author_facet | Souad Daamouch Sylvia Thiele Lorenz Hofbauer Martina Rauner |
| author_sort | Souad Daamouch |
| collection | DOAJ |
| description | The link between obesity and low bone strength has become a significant medical concern. The canonical Wnt signaling pathway is a key regulator of mesenchymal stem cell differentiation into either osteoblasts or adipocytes with active Wnt signaling promoting osteoblastogenesis. Our previous research indicated that Dickkopf-1 (Dkk1), a Wnt inhibitor, is upregulated in bone tissue in obesity and that osteoblast-derived Dkk1 drives obesity-induced bone loss. However, Dkk1 is also produced by adipocytes, but the impact of adipogenic Dkk1 on bone remodeling and its role in obesity-induced bone loss remain unclear. Thus, in this study, we investigated the influence of adipogenic Dkk1 on bone homeostasis and obesity-induced bone loss in mice. To that end, deletion of Dkk1 in adipocytes was induced by tamoxifen administration into 8-week-old male Dkk1fl/fl; AdipoQcreERT2 mice. Bone and fat mass were analyzed at 12 and 20 weeks of age. Obesity was induced in 8-week-old male Dkk1fl/fl;AdipoQcre mice with a high-fat diet (HFD) rich in saturated fats for 12 weeks. We observed that 12-week-old male mice without adipogenic Dkk1 had a significant increase in trabecular bone volume in the vertebrae and femoral bones. While histological and serological bone formation markers were not different, the number of osteoclasts and adipocytes was decreased in the vertebral bones of Dkk1fl/fl; AdipoQcre-positive mice. Despite the increased bone mass in 12-week-old male mice, at 20 weeks of age, there was no difference in the bone volume between the controls and Dkk1fl/fl; AdipoQcre-positive mice. Also, Dkk1fl/fl;AdipoQcre-positive mice were not protected from HFD-induced bone loss. Even though mRNA expression levels of Sost, another important Wnt inhibitor, in bone from Dkk1-deficient mice fed with HFD were decreased compared to Dkk1-sufficient mice on an HFD, this did not prevent the HFD-induced suppression of bone formation. In conclusion, adipogenic Dkk1 may play a transient role in bone mass regulation during adolescence, but it does not contribute to bone homeostasis or obesity-induced bone loss later in life. |
| first_indexed | 2024-03-11T19:59:28Z |
| format | Article |
| id | doaj.art-60f464f3a1b44dc4a9cf4396b22a412f |
| institution | Directory Open Access Journal |
| issn | 2049-3614 |
| language | English |
| last_indexed | 2024-03-11T19:59:28Z |
| publishDate | 2023-10-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-60f464f3a1b44dc4a9cf4396b22a412f2023-10-04T10:42:51ZengBioscientificaEndocrine Connections2049-36142023-10-011211112https://doi.org/10.1530/EC-23-0251Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male miceSouad Daamouch0Sylvia Thiele1Lorenz Hofbauer2Martina Rauner3Department of Medicine III and Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyDepartment of Medicine III and Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyDepartment of Medicine III and Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyDepartment of Medicine III and Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyThe link between obesity and low bone strength has become a significant medical concern. The canonical Wnt signaling pathway is a key regulator of mesenchymal stem cell differentiation into either osteoblasts or adipocytes with active Wnt signaling promoting osteoblastogenesis. Our previous research indicated that Dickkopf-1 (Dkk1), a Wnt inhibitor, is upregulated in bone tissue in obesity and that osteoblast-derived Dkk1 drives obesity-induced bone loss. However, Dkk1 is also produced by adipocytes, but the impact of adipogenic Dkk1 on bone remodeling and its role in obesity-induced bone loss remain unclear. Thus, in this study, we investigated the influence of adipogenic Dkk1 on bone homeostasis and obesity-induced bone loss in mice. To that end, deletion of Dkk1 in adipocytes was induced by tamoxifen administration into 8-week-old male Dkk1fl/fl; AdipoQcreERT2 mice. Bone and fat mass were analyzed at 12 and 20 weeks of age. Obesity was induced in 8-week-old male Dkk1fl/fl;AdipoQcre mice with a high-fat diet (HFD) rich in saturated fats for 12 weeks. We observed that 12-week-old male mice without adipogenic Dkk1 had a significant increase in trabecular bone volume in the vertebrae and femoral bones. While histological and serological bone formation markers were not different, the number of osteoclasts and adipocytes was decreased in the vertebral bones of Dkk1fl/fl; AdipoQcre-positive mice. Despite the increased bone mass in 12-week-old male mice, at 20 weeks of age, there was no difference in the bone volume between the controls and Dkk1fl/fl; AdipoQcre-positive mice. Also, Dkk1fl/fl;AdipoQcre-positive mice were not protected from HFD-induced bone loss. Even though mRNA expression levels of Sost, another important Wnt inhibitor, in bone from Dkk1-deficient mice fed with HFD were decreased compared to Dkk1-sufficient mice on an HFD, this did not prevent the HFD-induced suppression of bone formation. In conclusion, adipogenic Dkk1 may play a transient role in bone mass regulation during adolescence, but it does not contribute to bone homeostasis or obesity-induced bone loss later in life.https://ec.bioscientifica.com/view/journals/ec/12/11/EC-23-0251.xmldickkopf-1adipocytesbone losshigh-fat dietobesity |
| spellingShingle | Souad Daamouch Sylvia Thiele Lorenz Hofbauer Martina Rauner Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice Endocrine Connections dickkopf-1 adipocytes bone loss high-fat diet obesity |
| title | Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice |
| title_full | Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice |
| title_fullStr | Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice |
| title_full_unstemmed | Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice |
| title_short | Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice |
| title_sort | effects of adipocyte specific dkk1 deletion on bone homeostasis and obesity induced bone loss in male mice |
| topic | dickkopf-1 adipocytes bone loss high-fat diet obesity |
| url | https://ec.bioscientifica.com/view/journals/ec/12/11/EC-23-0251.xml |
| work_keys_str_mv | AT souaddaamouch effectsofadipocytespecificdkk1deletiononbonehomeostasisandobesityinducedbonelossinmalemice AT sylviathiele effectsofadipocytespecificdkk1deletiononbonehomeostasisandobesityinducedbonelossinmalemice AT lorenzhofbauer effectsofadipocytespecificdkk1deletiononbonehomeostasisandobesityinducedbonelossinmalemice AT martinarauner effectsofadipocytespecificdkk1deletiononbonehomeostasisandobesityinducedbonelossinmalemice |