Bmp7-KO Mouse

Bmp7, a member of the transforming growth factor-β (TGF-β) superfamily, is an extracellular signalling protein with diverse functions [5]. It is involved in multiple biological processes such as tissue regeneration, cell differentiation, and fibrosis regulation. Bmp7 exerts its effects through signalling pathways like Smad 1,5,9(8), p38, JNK MAP kinase, and STAT3 [2,4]. It plays a crucial role in the development and homeostasis of various organs, highlighting its overall biological importance. Genetic models, especially KO/CKO mouse models, have been instrumental in studying its functions.

In KO mouse models, Bmp7 has been shown to be essential for nephron development. Absence of Bmp7 reduces nephron number to one-tenth of its normal value and affects postnatal proximal tubule cell proliferation [4]. In the context of diseases, BMP7-loaded human umbilical cord mesenchymal stem cell-derived small extracellular vesicles can target activated hepatic stellate cells to ameliorate liver fibrosis [3]. BMP7 also reduces the fibrocartilage chondrocyte phenotype, potentially making it a disease-modifying molecule for osteoarthritis [1]. Additionally, it attenuates neuroinflammation after spinal cord injury by suppressing microglia activation and promoting M2 polarization via the STAT3 pathway [2]. High BMP7 expression is associated with poor prognosis in ovarian cancer [5].

In conclusion, Bmp7 is vital for normal organ development, especially in determining nephron number in the kidney. In disease research, Bmp7 KO/CKO mouse models have revealed its potential roles in fibrosis-related diseases like liver fibrosis and osteoarthritis, as well as in neuroinflammatory conditions post-spinal cord injury and in ovarian cancer prognosis. These findings highlight Bmp7's importance in understanding disease mechanisms and developing potential therapies.

References:

1. Ripmeester, Ellen G J, Caron, Marjolein M J, van den Akker, Guus G H, van Rhijn, Lodewijk W, Welting, Tim J M. 2021. BMP7 reduces the fibrocartilage chondrocyte phenotype. In Scientific reports, 11, 19663. doi:10.1038/s41598-021-99096-0. https://pubmed.ncbi.nlm.nih.gov/34608249/

2. Wei, Xiaojin, Huang, Chaodong, Chen, Kai, Yang, Lin, Wang, Yaping. 2023. BMP7 Attenuates Neuroinflammation after Spinal Cord Injury by Suppressing the Microglia Activation and Inducing Microglial Polarization Via the STAT3 Pathway. In Neurochemical research, 48, 2687-2700. doi:10.1007/s11064-023-03930-y. https://pubmed.ncbi.nlm.nih.gov/37071344/

3. Zhu, Dan, Sun, Zongbin, Wei, Jiayun, Lin, Yan, Li, Xun. 2024. BMP7-Loaded Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorate Liver Fibrosis by Targeting Activated Hepatic Stellate Cells. In International journal of nanomedicine, 19, 3475-3495. doi:10.2147/IJN.S450284. https://pubmed.ncbi.nlm.nih.gov/38623080/

4. Taglienti, Mary, Graf, Daniel, Schumacher, Valerie, Kreidberg, Jordan A. 2022. Bmp7 drives proximal tubule expansion and determines nephron number in the developing kidney. In Development (Cambridge, England), 149, . doi:10.1242/dev.200773. https://pubmed.ncbi.nlm.nih.gov/35877077/

5. Vasan, Richa, Yadav, Jahnavi, Aiyappa-Maudsley, Radhika, Storr, Sarah J, Martin, Stewart G. 2023. High BMP7 expression is associated with poor prognosis in ovarian cancer. In Journal of cellular and molecular medicine, 27, 3378-3387. doi:10.1111/jcmm.17951. https://pubmed.ncbi.nlm.nih.gov/37688374/