Disease relevance of Bmp1

• The role of TGF-beta/bone morphogenetic protein signaling in the chondrogenic differentiation of human synovial fibroblasts (SFs) was examined with the adenovirus vector-mediated gene transduction system [1].
• The ability to enhance BMP signaling while suppressing TGF-beta activation indicates a critical role for KCP in modulating the responses between these anti- and profibrotic cytokines in the initiation and progression of renal interstitial fibrosis [2].
• The bone morphogenetic protein (BMP)2 gene has been genetically linked to osteoporosis and osteoarthritis [3].
• The spinal neural tube defect results from a different mechanism: increased BMP signaling in the mesoderm between the limb buds leads to abnormal somite differentiation and axial skeletal malformation [4].
• Modulator of bone morphogenetic protein activity in the progression of kidney diseases [5].

Psychiatry related information on Bmp1

• Mice without water deprivation were given PCP or saline before a training trial, which consisted of exposure to a novel open-field environment with an alcove containing a water tube [6].
• Thirty-eight analogues of 1-phenylcyclohexylamine (PCA), a phencyclidine (PCP) derivative, were examined for their activities in the mouse maximal electroshock (MES) seizure test and in a motor-toxicity assay [7].
• 5. Pretreatment with PCP (3-30 mg kg-1) or MK-801 (0.1-1.6 mg kg-1) significantly increased locomotor activity in mice [8].
• There was a significant inverse relationship between the step-down and escape latencies, indicating that PCP had induced amnesia [9].
• OBJECTIVE: To investigate how the background genotype contributes to glutamate's effects on attention and response control, we examined how phencyclidine (PCP) affected the performance of a five-choice serial reaction time (5-CSRT) task in two inbred mouse strains, C57BL/6N and DBA/2N [10].

High impact information on Bmp1

• Because Bmpr1a is evolutionarily conserved, these findings indicate that a component of the BMP signaling pathway has been co-opted during evolution for male sexual development in amniotes [11].
• Bone morphogenetic protein (BMP) controls osteoblast proliferation and differentiation through Smad proteins [12].
• The mouse short ear skeletal morphogenesis locus is associated with defects in a bone morphogenetic member of the TGF beta superfamily [13].
• Chordin and Noggin are secreted bone morphogenetic protein (BMP) antagonists expressed in the mouse node, but not in the AVE [14].
• The physiological importance of the BMP system for mammalian reproduction has been further highlighted by the elucidation of the aberrant reproductive phenotypes of animals with naturally occurring mutations or targeted deletions of certain BMP family genes [15].

Chemical compound and disease context of Bmp1

• Whereas it was thought that estrogens work exclusively by inhibiting bone resorption, our previous results show that 17beta-estradiol (E2) increases mouse bone morphogenetic protein (BMP)-2 mRNA, suggesting that estrogens may also enhance bone formation [16].
• Furthermore, phencyclidine (PCP) (2 mg/kg) can selectively induce social withdrawal in naive rats that were housed in pairs (familiar) for 10 days prior to testing without affecting motor activity [17].
• In the present experiment, locomotor activity and performance on an inverted screen test in untrained mice were used to differentiate PCP-type non-competitive NMDA antagonists from other drug classes [18].
• This baseline was explored using three manipulations employed in the clinical management of PCP toxicity: treatment with a neuroleptic (haloperidol), a benzodiazepine (chlordiazepoxide) and modification in environmental stimulation (changing of lighting conditions) [19].
• These uncompetitive NMDA antagonists [PCP, dizocilpine, (-)-MK-801, TCP, (+)-SKF 10,047, dextrorphan, ketamine] produced dose-related increases in locomotor activity and the percentage of mice falling off an inverted, elevated wire mesh screen [18].

Biological context of Bmp1

• We have disrupted the mouse Bmp1 gene by deleting DNA sequences encoding the active site of the astacin-like protease domain common to all splice variants [20].
• Bone morphogenetic protein (BMP) signaling regulates body axis determination, apoptosis, and differentiation of various types of cells including neuron, gut, and bone cells [21].
• Negative regulation of bone morphogenetic protein/Smad signaling by Cas-interacting zinc finger protein in osteoblasts [21].
• Knockdown of BMP1 expression results in a mild tail phenotype [22].
• Here we report the use of a cDNA library, prepared from BMP-1/mTld-null mouse embryos, to isolate cDNA clones for a novel mammalian protein with a domain structure identical to that of mTld [23].

Anatomical context of Bmp1

• Twisted Gastrulation Modulates Bone Morphogenetic Protein-induced Collagen II and X Expression in Chondrocytes in Vitro and in Vivo [24].
• Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures [25].
• BMP receptor type IA in limb bud mesenchyme regulates distal outgrowth and patterning [26].
• Using the Cre/loxP system in mice, we rendered limb bud mesenchyme insensitive to BMP signals through the type I receptor, BMPR-IA [26].
• Inhibins differentially antagonize activin and bone morphogenetic protein action in a mouse adrenocortical cell line [27].

Associations of Bmp1 with chemical compounds

• Here, we show that BMP-1 cleaves probiglycan at a single site, removing the propeptide and producing a biglycan molecule with an NH(2) terminus identical to that of the mature form found in tissues [28].
• We report here that significant osteogenesis, as determined by gene expression and histological analysis, is induced only when mouse ADAS are cultured in the presence of retinoic acid with or without recombinant human bone morphogenetic protein (BMP)-2 supplementation [29].
• Studies have shown that the minimal structure for procollagen proteinase activity is proteinase-CUB1-CUB2 (BMP-1DeltaEC3) and therefore lacking the epidermal growth factor (EGF)-like domain thought to account for the Ca(2+) dependence of BMP-1 [30].
• Collectively, these findings provide novel insights into BMP action and demonstrate that BMP signaling governs the fate of prechondrogenic mesenchyme, at least in part, through regulation of retinoid signaling [31].
• Type I procollagen COOH-terminal proteinase (C-proteinase) enhancer, a glycoprotein that binds to the COOH-terminal propeptide of type I procollagen and enhances procollagen C-proteinase activity, was purified from mouse fibroblast culture media [32].

Physical interactions of Bmp1

• Suv39h histone methyltransferases interact with Smads and cooperate in BMP-induced repression [33].

Regulatory relationships of Bmp1

• BMP-induced Smad1 and Smad5 activation of GCCG-mediated transcription was blocked in the presence of CIZ overexpression [21].
• Here we show that the 36 kDa, active fragment of PCPE enhances the activity of both the short (mouse) and long (chick) forms of PCP/BMP-1 [34].
• The mammalian bone morphogenetic protein-1 (BMP-1)/Tolloid-related metalloproteinases play key roles in regulating formation of the extracellular matrix (ECM) via biosynthetic processing of various precursor proteins into mature functional enzymes, structural proteins, and proteins involved in initiating the mineralization of hard tissue ECMs [35].
• These data show that BMP9 activates the canonical BMP signaling pathway and suggest that this could be one of the mechanisms responsible for the induction of the cholinergic phenotype by BMP9 in the basal forebrain [36].
• Pax3 regulates morphogenetic cell behavior in vitro coincident with activation of a PCP/non-canonical Wnt-signaling cascade [37].

Other interactions of Bmp1

• The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart [38].
• These data indicate that CIZ is a novel type inhibitor of BMP/Smad signaling [21].
• Bone morphogenetic protein-1/tolloid-related metalloproteinases process osteoglycin and enhance its ability to regulate collagen fibrillogenesis [35].
• Finally, when the amount of PCP is adjusted so that the rate of C-terminal processing remains constant, PCPE (36 kDa) has no effect on the assembly of collagen or pN-collagen in vitro following C-terminal processing of the corresponding precursors [34].
• These results provide limited support for the anti-BMP model of inhibin action and reveal that, relative to inhibin A, inhibin B essentially behaves as a selective activin antagonist in AC cells [27].

Analytical, diagnostic and therapeutic context of Bmp1

• In situ hybridizations show the distribution of mTll RNA to overlap extensively that previously shown for the BMP-1 and mTld RNA forms [23].
• Detection of multiple bone morphogenetic protein messenger ribonucleic acids and their signal transducer, Smad1, during mouse decidualization [39].
• In vivo xenograft studies in the flanks of nude mice confirmed that the BMP-treated cells were significantly less tumorigenic than untreated cells [40].
• Phosphorylation of mothers against decapentaplegic homolog 1 (Smad1) and bone morphogenetic protein (BMP)-like molecules in EMD was determined by Western blot [41].
• We also investigated the effect of the BMP antagonist noggin in vivo in mice by assessing colon tissue with immunohistochemistry and immunoblotting [42].

References