Disease relevance of BMP7

• Immunohistochemistry of primary and metastatic melanoma also shows increased BMP4 and BMP7 expression compared with nevi [1].
• In the bone metastasis-derived PC-3 prostate cancer cells, BMP7 induced epithelial-mesenchymal transdifferentiation with classic changes in morphology, motility, invasiveness, and molecular markers [2].
• Considerable evidences have accumulated to demonstrate that BMP7, a member of the BMP superfamily, attenuates TGFbeta-induced interstitial fibrosis by a reverse of transdifferentiation of renal tubular epithelial cells into mesenchymal cells [3].
• METHODS: AAV-BMP7 was packaged by infecting the stable cell clone BHK-21 (integrated with recombinant AAV vector plasmid pSNAV-BMP7) with recombinant herpes simplex virus type 1, which expresses AAV-2 Rep and Cap and possesses AAV packaging functions [4].
• In the ossifying center of the bone rudiments, both OP-1 and TGF-beta inhibited cartilage hypertrophy, growth of the bone collar, and matrix mineralization [5].
• BMP7 can still counteract the epithelial-to-mesenchymal transition process in the metastatic tumor, positioning BMP7 as a novel therapeutic molecule for treatment of metastatic bone disease [6].

Psychiatry related information on BMP7

• The higher BMD at weight-bearing sites in badminton players compared with ice hockey players, despite significantly less average weekly training, indicates that physical activity including jumps in unusual directions has a great osteogenic potential [7].
• Proceedings of the Osteosarcoma Study Group Meeting (Bethesda, Maryland, January 19, 1977): introduction: treatment of osteogenic sarcoma [8].

High impact information on BMP7

• Long-term remission, with local control rates of 50 to 70 percent, have been reported in a number of very large osteogenic sarcomas, soft tissue sarcomas, melanomas, and adenocarcinomas of the alimentary tract [9].
• Cooperation of BMP7 and SHH in the induction of forebrain ventral midline cells by prechordal mesoderm [10].
• Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva [11].
• BMP4 and BMP7 are expressed in the epidermal ectoderm, and both proteins mimic its inductive activity [12].
• We examined echocardiograms from 120 children and adults who had received cumulative doses of 244 to 550 mg of doxorubicin per square meter of body-surface area for the treatment of acute lymphoblastic leukemia or osteogenic sarcoma in childhood, a mean of 8.1 years earlier [13].

Chemical compound and disease context of BMP7

• We have recently demonstrated that phenytoin, a widely used therapeutic agent for seizure disorders, has osteogenic effects in rats and in humans in vivo, and in human bone cells in vitro [14].
• The OP-1 injection to the degenerative disc stimulated an anabolic response characterized by the restoration of the normal morphology of the disc, increased Safranin O staining in the NP, extention of the extracellular matrix, and stimulation of endogenous OP-1 synthesis in the NP, annulus fibrosis (AF), and end-plate [15].
• SUMMARY OF BACKGROUND DATA: Osteogenic protein-1 is a potential bone graft alternative that has achieved high fusion rates in a rabbit lumbar fusion model, including in the repair of nicotine-induced pseudarthroses [16].
• As the phosphoinositide cascade and, particularly, the calcium-mobilizing inositol 1,4,5-trisphosphate (InsP3) receptor are integral to stimulus-secretion coupling in osteoblasts, the hypothesis that BMP-7 affects InsP3 receptor expression was examined in the G-292 human osteosarcoma cell line and in primary cultures of human osteoblasts [17].
• In the present study, we show that BMP-7 inhibits the proliferation of androgen-insensitive PC-3 and DU-145 prostate cancer cells in a medium containing 1% fetal bovine serum, observed as decreased incorporation of [(3)H]thymidine and decreased cell number [18].

Biological context of BMP7

• One extrinsic factor, BMP7, has been shown to specifically affect dendritic morphogenesis; however, the underlying mechanism by which this occurs is unknown [19].
• Thus, our results reveal a strikingly specific antagonism of BMP7-mediated processes by myostatin and suggest that myostatin is an important regulator of adipogenesis [20].
• Finally, BMP7 inhibited serum starvation-induced apoptosis in the LNCaP prostate cancer cell line and more remarkably in its bone metastatic variant C4-2B line [2].
• In all cases, BMP7 induced Smad phosphorylation in a dose-dependent manner, with Smad5 activation clearly demonstrable [2].
• In this study, combined BMP2 and BMP7 gene transfer was performed to test whether this approach improves osteoblastic differentiation and bone formation compared with single BMP gene transfer [21].

Anatomical context of BMP7

• In the presence of BMP7, inhibition of alpha5beta1 integrin function still induced the formation of the ectopic joint between proliferating chondrocytes and hypertrophic chondrocytes [22].
• To determine the relevance of this finding to human prostate cancer, we examined the expression of BMPs and BMP receptors (BMPR) as well as the responsiveness to recombinant human BMP7 in a series of human prostate tumor cell lines [2].
• Our results suggest that 1,25(OH)2-vitamin D3 modulates in opposite ways the effects of BMP7 and TGFbeta1 on osteoblast differentiation [23].
• We tested the hypothesis that BMP7 functions by antagonizing profibrogenic events that are induced by transforming growth factor (TGF)-beta in cultured mesangial cells [24].
• We examined the effects of TGF-beta1, -beta2, BMP2, BMP7 on five epithelial cell lines in vitro [25].

Associations of BMP7 with chemical compounds

• These results suggest that E2 and BPA suppress estrogen-dependent apoptosis of epithelial cells of the endometrium through down-regulation of actRIIB and BMP7 [26].
• Repeated treatment with E2 resulted in decreased expression of both actRIIB and BMP7 mRNA in the uteri of ovariectomized mice [26].
• A single oral administration of bisphenol A (BPA), an environmental estrogen, inhibited actRIIB and BMP7 expression and apoptosis in the luminal epithelium of the mouse uterus at diestrus (or early proestrus) [26].
• We found that OP-1 stimulated cartilage growth as determined by sulfate incorporation and that it increased remarkably the width of the long bones ends compared with controls [5].
• In serum-free conditions, OP-1 promoted cell proliferation and chondrocyte maturation, without requiring either thyroid hormone or insulin, agents known to support chick chondrocyte differentiation in vitro [27].

Physical interactions of BMP7

• Endoglin did not interact with BMP-7 through complexes containing the BMP type II receptor, demonstrating specificity of its action [28].
• Together, our findings suggest that MEF promotes cell proliferation and functions as a negative regulator of osteogenic differentiation by directly interacting with Runx2 and suppressing its transcriptional activity [29].
• Enhanced osteogenic promotion around dental implants with synthetic binding motif mimicking bone morphogenetic protein (BMP)-2 [30].
• Expression of transferrin and vitamin D-binding protein genes in an osteogenic sarcoma cell line [31].
• We measured urinary levels of total protein, N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase, and adenosine deaminase-binding protein in ten children with osteogenic sarcoma who were receiving combination chemotherapy that included 12 doses of methotrexate (12 g/m2) [32].

Co-localisations of BMP7

• Phospho-Smads 1/5/8 and ID1 expression largely colocalized with BMP-7 and was also localized in the epithelia of the distal tubule and the CDs [33].

Regulatory relationships of BMP7

• Basic fibroblast growth factor inhibits the anabolic activity of insulin-like growth factor 1 and osteogenic protein 1 in adult human articular chondrocytes [34].
• Osteogenic differentiation of human mesenchymal stem cells is regulated by bone morphogenetic protein-6 [35].
• Undecalcified sections cut for histological analysis 60 d after healing of hOP-1-treated specimens showed substantial cementogenesis with scattered remnants of the collagenous carrier. hBMP-2 applied alone induced greater amounts of mineralized bone and osteoid when compared to hOP-1 alone or to combined morphogen applications [36].
• OP-1 treatment stimulated mRNA expression of BMPR-IA and BMPR-II, but had little effect on ActR-I and BMPR-IB mRNA expression [37].
• Osteogenic differentiation induced by bone morphogenetic proteins can be suppressed by platelet-released supernatant in vitro [38].

Other interactions of BMP7

• Binding of OP-1/BMP-7 to BMPR-II was also observed in nontransfected cell lines [39].
• METHODS: Human articular chondrocytes were cultured in alginate beads or as cartilage explants in serum-free medium with or without IGF-1 (100 ng/ml), OP-1 (100 ng/ml), or bFGF (0-100 ng/ml) [34].
• Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat [40].
• In contrast, changes in BMP5 and BMP7 expression in the perichondrium correspond to altered differentiation states of the flanking chondrocytes [41].
• As BMP-7 is expressed in the adult human TM in situ, it seems reasonable to assume that it similarly modulates and antagonizes the effects of TGF-beta2 signaling on the tissues of the outflow pathways in vivo [42].

Analytical, diagnostic and therapeutic context of BMP7

• BMP7 stimulation led to a decrease of 1,25(OH)2-vitamin D3-induced binding of nuclear proteins to a vitamin D response element, as shown by electrophoretic mobility shift assay [23].
• Bioassays revealed that FSH enhances BMP-induced SMAD1/5/8 phosphorylation and cellular DNA synthesis induced by BMP6 and BMP7 [43].
• Seven BMP cDNAs (BMP1 through BMP7) have been recovered through molecular cloning [44].
• Evaluation of hOP-1 effects on cell growth and collagen synthesis in rat osteoblast-enriched bone cell cultures showed that both cell proliferation and collagen synthesis were stimulated in a dose-dependent manner and increased 3-fold in response to 40 ng of hOP-1/ml [45].
• METHODS: Transcription of activin and receptors (ActR) for activin A and BMP-7 was detected by RT-PCR [46].

References