Bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-β (TGF-β) superfamily, is a pluripotent factor with essential roles in embryonic development and postnatal tissue and organ homeostasis. It is involved in multiple biological processes such as osteogenesis, adipogenesis, chondrogenesis, and myogenesis, influencing the differentiation of mesenchymal cells [1,7].

BMP2 has been implicated in various disease conditions. In cancer, it can promote cancer cell bone metastasis by inducing macrophages to differentiate into osteoclasts and accelerating the osteolytic mechanism [1]. In lung adenocarcinoma, it promotes metastasis through BMP receptor 2-mediated SMAD1/5 activation, and depletion of BMP2 or its receptor reduces cell migration and invasiveness [2]. In a family with BMP2 haploinsufficiency, a novel frameshift variant was associated with short stature, hearing impairment, minor skeletal deformities, and isolated dextrocardia situs solitus [3]. Regarding bone-related diseases, BMP2 is crucial for bone formation and repair [4], and it can induce the osteogenic differentiation of mesenchymal stem cells, which is significant for preventing and treating osteoporosis [5,6]. In breast cancer cells, BMP2 enhances an adipocyte-like property [8], and in gynecologic cancer cells, it promotes tumorigenic signaling through the induction of FN14 [9]. In the female reproductive system, BMP2 suppresses the production of pentraxin 3 in endometrial stromal and decidual stromal cells, potentially regulating endometrial decidualization [10].

In conclusion, BMP2 is a key factor in multiple biological processes and is associated with various diseases, including cancer, bone-related disorders, and female reproductive-related conditions. Studies, especially those using gene-knockout or conditional-knockout mouse models, have significantly enhanced our understanding of BMP2's functions and its role in disease development, providing potential therapeutic targets for these diseases.