PRDM16 Enhances Osteoblastogenic RUNX2 via Canonical WNT10b/β-CATENIN Pathway in Testosterone-Treated Hypogonadal Men
We previously reported that <i>PRDM16</i> mediated the improvement in body composition in testosterone (T)-treated hypogonadal men by shifting adipogenesis to myogenesis. Previous preclinical studies suggest that <i>Prdm16</i> regulates <i>Runx2</i>, an important...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/15/1/79 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588896590888960 |
|---|---|
| author | Siresha Bathina Mia Prado Virginia Fuenmayor Lopez Georgia Colleluori Lina Aguirre Rui Chen Dennis T. Villareal Reina Armamento-Villareal |
| author_facet | Siresha Bathina Mia Prado Virginia Fuenmayor Lopez Georgia Colleluori Lina Aguirre Rui Chen Dennis T. Villareal Reina Armamento-Villareal |
| author_sort | Siresha Bathina |
| collection | DOAJ |
| description | We previously reported that <i>PRDM16</i> mediated the improvement in body composition in testosterone (T)-treated hypogonadal men by shifting adipogenesis to myogenesis. Previous preclinical studies suggest that <i>Prdm16</i> regulates <i>Runx2</i>, an important osteoblastic transcription factor, expression and activity. However, the changes in <i>PRDM16</i>, and other genes/proteins involved in osteoblastogenesis with T therapy in hypogonadal men are unexplored. We investigated the role of PRDM16 in RUNX2 activation by measuring changes in gene expression in peripheral blood monocytes (PBMCs) and proteins in the serum of hypogonadal men after T therapy for 6 months. Likewise, we evaluated changes in the WNT10b—β-CATENIN signaling pathway by gene expression and protein analyses. We found significant increases in <i>PRDM16</i> and <i>RUNX2</i> expression in PBMCs together with significant increases in serum proteins at 6 months when compared to baseline. There were also increases in gene and protein expressions of WNT10b, and β-CATENIN at 6 months. Furthermore, we found a significant positive correlation between % changes in PRDM16 and WNT10b. Our results suggest that T therapy activates PRDM16, leading to enhanced signaling in the canonical WNT10b—β-CATENIN-RUNX2 pathway, the pathway involved in osteoblastogenesis. The above findings may account for the improvement in bone density and quality in hypogonadal men treated with T. |
| format | Article |
| id | doaj-art-3c9b5e09795a4476acb687f42fd3e033 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-3c9b5e09795a4476acb687f42fd3e0332025-01-24T13:25:06ZengMDPI AGBiomolecules2218-273X2025-01-011517910.3390/biom15010079PRDM16 Enhances Osteoblastogenic RUNX2 via Canonical WNT10b/β-CATENIN Pathway in Testosterone-Treated Hypogonadal MenSiresha Bathina0Mia Prado1Virginia Fuenmayor Lopez2Georgia Colleluori3Lina Aguirre4Rui Chen5Dennis T. Villareal6Reina Armamento-Villareal7Division of Endocrinology Diabetes and Metabolism, Baylor College of Medicine, Houston, TX 77030, USADivision of Endocrinology Diabetes and Metabolism, Baylor College of Medicine, Houston, TX 77030, USADivision of Endocrinology Diabetes and Metabolism, Baylor College of Medicine, Houston, TX 77030, USADivision of Endocrinology Diabetes and Metabolism, Baylor College of Medicine, Houston, TX 77030, USADepartment of Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87107, USADivision of Endocrinology Diabetes and Metabolism, Baylor College of Medicine, Houston, TX 77030, USADivision of Endocrinology Diabetes and Metabolism, Baylor College of Medicine, Houston, TX 77030, USADivision of Endocrinology Diabetes and Metabolism, Baylor College of Medicine, Houston, TX 77030, USAWe previously reported that <i>PRDM16</i> mediated the improvement in body composition in testosterone (T)-treated hypogonadal men by shifting adipogenesis to myogenesis. Previous preclinical studies suggest that <i>Prdm16</i> regulates <i>Runx2</i>, an important osteoblastic transcription factor, expression and activity. However, the changes in <i>PRDM16</i>, and other genes/proteins involved in osteoblastogenesis with T therapy in hypogonadal men are unexplored. We investigated the role of PRDM16 in RUNX2 activation by measuring changes in gene expression in peripheral blood monocytes (PBMCs) and proteins in the serum of hypogonadal men after T therapy for 6 months. Likewise, we evaluated changes in the WNT10b—β-CATENIN signaling pathway by gene expression and protein analyses. We found significant increases in <i>PRDM16</i> and <i>RUNX2</i> expression in PBMCs together with significant increases in serum proteins at 6 months when compared to baseline. There were also increases in gene and protein expressions of WNT10b, and β-CATENIN at 6 months. Furthermore, we found a significant positive correlation between % changes in PRDM16 and WNT10b. Our results suggest that T therapy activates PRDM16, leading to enhanced signaling in the canonical WNT10b—β-CATENIN-RUNX2 pathway, the pathway involved in osteoblastogenesis. The above findings may account for the improvement in bone density and quality in hypogonadal men treated with T.https://www.mdpi.com/2218-273X/15/1/79PRDM16RUNX2osteoblastogenesisBMD |
| spellingShingle | Siresha Bathina Mia Prado Virginia Fuenmayor Lopez Georgia Colleluori Lina Aguirre Rui Chen Dennis T. Villareal Reina Armamento-Villareal PRDM16 Enhances Osteoblastogenic RUNX2 via Canonical WNT10b/β-CATENIN Pathway in Testosterone-Treated Hypogonadal Men Biomolecules PRDM16 RUNX2 osteoblastogenesis BMD |
| title | PRDM16 Enhances Osteoblastogenic RUNX2 via Canonical WNT10b/β-CATENIN Pathway in Testosterone-Treated Hypogonadal Men |
| title_full | PRDM16 Enhances Osteoblastogenic RUNX2 via Canonical WNT10b/β-CATENIN Pathway in Testosterone-Treated Hypogonadal Men |
| title_fullStr | PRDM16 Enhances Osteoblastogenic RUNX2 via Canonical WNT10b/β-CATENIN Pathway in Testosterone-Treated Hypogonadal Men |
| title_full_unstemmed | PRDM16 Enhances Osteoblastogenic RUNX2 via Canonical WNT10b/β-CATENIN Pathway in Testosterone-Treated Hypogonadal Men |
| title_short | PRDM16 Enhances Osteoblastogenic RUNX2 via Canonical WNT10b/β-CATENIN Pathway in Testosterone-Treated Hypogonadal Men |
| title_sort | prdm16 enhances osteoblastogenic runx2 via canonical wnt10b β catenin pathway in testosterone treated hypogonadal men |
| topic | PRDM16 RUNX2 osteoblastogenesis BMD |
| url | https://www.mdpi.com/2218-273X/15/1/79 |
| work_keys_str_mv | AT sireshabathina prdm16enhancesosteoblastogenicrunx2viacanonicalwnt10bbcateninpathwayintestosteronetreatedhypogonadalmen AT miaprado prdm16enhancesosteoblastogenicrunx2viacanonicalwnt10bbcateninpathwayintestosteronetreatedhypogonadalmen AT virginiafuenmayorlopez prdm16enhancesosteoblastogenicrunx2viacanonicalwnt10bbcateninpathwayintestosteronetreatedhypogonadalmen AT georgiacolleluori prdm16enhancesosteoblastogenicrunx2viacanonicalwnt10bbcateninpathwayintestosteronetreatedhypogonadalmen AT linaaguirre prdm16enhancesosteoblastogenicrunx2viacanonicalwnt10bbcateninpathwayintestosteronetreatedhypogonadalmen AT ruichen prdm16enhancesosteoblastogenicrunx2viacanonicalwnt10bbcateninpathwayintestosteronetreatedhypogonadalmen AT dennistvillareal prdm16enhancesosteoblastogenicrunx2viacanonicalwnt10bbcateninpathwayintestosteronetreatedhypogonadalmen AT reinaarmamentovillareal prdm16enhancesosteoblastogenicrunx2viacanonicalwnt10bbcateninpathwayintestosteronetreatedhypogonadalmen |