Disease relevance of Bmpr2

• BMPR-II heterozygous mice have mild pulmonary hypertension and an impaired pulmonary vascular remodeling response to prolonged hypoxia [1].
• Organ culture of cartilage rudiments showed that chondrocyte hypertrophy induced by BMP2 was inhibited in cartilage prepared from Smad6 transgenic mice [2].
• Finally, using adenovirus mediated bone morphogenetic protein 2 (BMP-2) gene transfer into fracture site we showed accelerated up-regulation of the genes for all three Sox proteins and type II collagen in fractures treated with BMP-2 when compared with control fractures [3].
• BMPR-IB and BMPR-II have been reported to be expressed at low levels in prostate cancer [4].
• Treatment of isolated stem cell populations with soluble BMP-2, -4, and -7 induced dose-dependent changes in proliferation, clonogenicity, cell surface phenotype, and multilineage repopulation capacity after transplantation in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice [5].

High impact information on Bmpr2

• BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing [6].
• In fact, in bones lacking BMP2, the earliest steps of fracture healing seem to be blocked [6].
• Mice lacking the ability to produce BMP2 in their limb bones have spontaneous fractures that do not resolve with time [6].
• BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect [7].
• LIF and BMP2 were found to act in synergy on primary fetal neural progenitor cells to induce astrocytes [8].

Chemical compound and disease context of Bmpr2

• These results show that BMP-2/insulin treatment induces full differentiation toward hypertrophy, whereas treatment with PTH/dexamethasone slows and limits differentiation [9].

Biological context of Bmpr2

• At the late bell stage, BMP-2 or -4 may induce cell differentiation [10].
• Further investigation of the expression of these receptors in lenses of transgenic mice, which ectopically express a truncated TbetaRII, showed marked up regulation and aberrant expression of ALK3, but not BMPRII or ActRII [11].
• INTRODUCTION: The expression of bone morphogenetic protein receptors (BMPRs) and Noggin during ectopic bone formation after implantation of BMP-2 into the back muscles of adult mice was investigated in this study [12].
• A region encompassing the chondrocyte-specific enhancer, localized in intron I of type-II collagen alpha1 chain (Col2a1) gene, is sufficient to confer BMP-2-dependent transcriptional induction of type-II collagen gene expression [13].
• Taken together, these results indicate that SOX6 is an important downstream mediator of BMP-2 signaling in chondrogenesis [13].

Anatomical context of Bmpr2

• Here we report that the ablation of Bmpr2 in pulmonary artery smooth muscle cells, using an ex vivo conditional knock-out (Cre-lox) approach, as well as small interfering RNA specific for Bmpr2, does not abolish BMP signaling [14].
• BMPR-II mRNA exhibits peak expression within the cerebellar Purkinje cell layer and the hippocampus, as well as within cranial ganglia [15].
• In this study, in situ hybridization analyses demonstrate that BMP-specific type I (BMPR-IA and BMPR-IB) and type II (BMPR-II) receptor mRNAs are expressed at significant levels in multiple regions of the CNS, cranial ganglia, and peripheral sensory and autonomic ganglia during the embryonic and neonatal periods [15].
• The BMP type-II receptor (BMPR-II) ECD antagonised oocyte and GDF9 bioactivity dose-dependently, but had no or minimal effect on TGFbeta1 and activin-A bioactivity, demonstrating its specificity [16].
• Our results suggest that the function of BMPR-II is essential for epiblast differentiation and mesoderm induction during early mouse development [17].

Associations of Bmpr2 with chemical compounds

• Multipotential mouse embryonic mesenchymal cells, C3H10T1/2, were cultured on 2-dimensional P-C fibrils or 3-dimensional P-C/BMP-2-coated (P-C-B) PLA scaffolds [18].
• Recent studies from our lab indicate that when human bone marrow MSC are placed in primary culture, osteogenesis can be induced by dexamethasone (Dex), but not by BMP-2, -4, or -7 [19].
• The bioreactor was created by implanting an osteoconductive hydroxyapatite scaffold pre-loaded with saline as a control or with bone morphogenetic protein-2 (BMP-2) to the murine femoral artery [20].
• Compared with previous reports using a brief BMP-2 supplementation early in differentiation, prolonged exposure increased chondrogenic output, while supplementation with insulin and ascorbic acid prevented dedifferentiation [21].
• These findings provide the first evidence for an interaction between BMPR-II-mediated signaling and the serotonin pathway, perturbation of which may be critical to the pathogenesis of PAH [22].

Other interactions of Bmpr2

• C2C12 cells expressed BMPR-IA and BMPR-II mRNAs, but not BMPR-IB mRNA at detectable levels in Northern blotting [23].
• Here, we describe the pattern of expression of BMP receptors, including Bmpr-Ia, Bmpr-Ib, Bmpr-II, Actr-I [24].
• Loss-of-function mutations in Bmpr2 have been implicated in tumorigenesis and in the etiology of primary pulmonary hypertension [14].
• Renal expression of the high-affinity BMP type II receptor and the type I receptor Alk2 (activin receptor-like kinase-2) decreased [25].
• Chimeric receptors with transmembrane cytoplasmic domains of activin receptor type II and bone morphogenetic protein receptor type II also provided signals in conjunction with chimeric T beta RI [26].

Analytical, diagnostic and therapeutic context of Bmpr2

• To elucidate the function of BMPR-II in mammalian development, we generated BMPR-II mutant mice by gene targeting [17].
• This capacity of adenovirus-mediated overproduction of BMP-2 to induce chondrogenesis (and subsequent endochondral ossification) should be useful for tissue engineering of cartilage and bone [27].
• In vitro protein production was determined with luciferase assay or ELISA (for BMP-2 production) weekly for 12 weeks [28].
• The expression of BMPR-IB and BMPR-II mRNA was up-regulated by HGF, as shown by both conventional PCR and quantitative PCR [4].
• An elevation of BMPR-IB and BMPR-II at the protein level was confirmed by both Western blot analysis and immunocytochemical staining [4].

References