Disease relevance of Bmp6

• Both the fetal and adult compound-deficient mice showed a reduction in the trabecular bone volume with suppressed bone formation, but normal bone resorption, whereas the single deficient mice (Bmp2+/- or Bmp6-/-) did not [1].
• By puberty, ihh, bmp6 and gli transcripts were no longer detected in the growth plate, despite the fact that physeal chondrocytes continued to hypertrophy and differentiate [2].

High impact information on Bmp6

• The murine Vgr-1 (Vg-related) and BMP-2a (bone morphogenetic protein 2a) genes are members of the decapentaplegic subgroup of the transforming growth factor-beta (TGF beta) superfamily [3].
• Vgr-1 RNA is maternally encoded in ovarian oocytes but declines in fertilized eggs and is undectable by the two- to four-cell stage [3].
• Patterns of expression of murine Vgr-1 and BMP-2a RNA suggest that transforming growth factor-beta-like genes coordinately regulate aspects of embryonic development [3].
• From mid-gestation on, Vgr-1 RNA is expressed at high levels in developing skin, especially in the suprabasal cells of the proliferating epidermis but not in the dermis or hair follicles, both of which contain TGF beta 1 and/or TGF beta 2 RNAs [3].
• Overexpression of bone morphogenetic protein-6 (BMP-6) in the epidermis of transgenic mice: inhibition or stimulation of proliferation depending on the pattern of transgene expression and formation of psoriatic lesions [4].

Biological context of Bmp6

• In the present study, we describe the expression of Bmp6 and Bmp7 in overlapping and adjacent sites, including the cardiac cushions during mouse embryonic development [5].
• Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration [6].
• Strong and uniform expression of the BMP-6 transgene resulted in severe repression of cell proliferation in embryonic and perinatal epidermis but had marginal effects on differentiation [4].
• Involvement of Bone Morphogenetic Protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse [7].
• Using primary pituitary cell cultures derived from transgenic mice that carry the ovine FSHbeta promoter linked to a luciferase reporter gene (oFSHbetaLuc), BMP-7 or BMP-6 was found to stimulate oFSHbetaLuc expression by 6-fold [8].

Anatomical context of Bmp6

• The defects in sternum development in Bmp6 null mice are likely to be associated with a transient early expression of Bmp6 in the sternal bands, prior to ossification [9].
• This study initially investigated expression patterns of BMPs in the mouse long bone and found that BMP2 and BMP6 were the main subtypes expressed in hypertrophic chondrocytes that induce endochondral bone formation [1].
• In contrast, osteoblasts were consistently BMP-6 negative [10].
• In untreated animals, BMP-6 was expressed by a significant proportion of growth plate chondrocytes and a subpopulation of bone marrow cells [10].
• We conclude that estrogen-induced osteogenesis in female mice is associated with increased levels of BMP-6 mRNA in mouse femurs, which seems to reflect the emergence of clusters of BMP-6 positive stromal cells adjacent to active bone formation surfaces [10].

Associations of Bmp6 with chemical compounds

• Increased bone morphogenetic protein-6 expression in mouse long bones after estrogen administration [10].
• Inhibition of adipogenic differentiation by apigenin could be due to induction of osteogensis as it robustly upregulates mRNA levels of bone morphogenetic protein-6 (BMP-6) [11].

Regulatory relationships of Bmp6

• Double immunolabeling studies revealed that only approximately 10% of BMP-6-positive bone marrow cells co-expressed the osteoblast transcription factor Cbfa1 suggesting that they are largely distinct from the osteoblast precursor population generated concurrently [10].
• Ca2+ and BMP-6 signaling regulate E2F during epidermal keratinocyte differentiation [12].

Other interactions of Bmp6

• We thus concluded that endogenous BMP2 and BMP6 cooperatively play pivotal roles in bone formation under both physiological and pathological conditions [1].
• Although bmp6 was expressed, ihh transcripts were not found in primordia of intramembranous bones, nor in cells lining the future articular surfaces [2].
• Based on knockout mouse models BMP-6 does not play an essential role in ovarian function, but GDF-9 is absolutely required for preantral follicle development [13].
• Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points [6].
• In contrast, misexpression of BMP-6 resulted in complete agenesis of the pancreas and reduced the size of the stomach and spleen dramatically and caused fusion of the liver and duodenum [14].

Analytical, diagnostic and therapeutic context of Bmp6

• To evaluate roles for Bmp6 signaling in vivo, gene targeting was used to generate a null mutation at the Bmp6 locus [9].
• Estrogen-induced changes in BMP-6 protein expression were assessed by immunocytochemistry in longitudinal femoral sections [10].
• Therefore, we investigated the expression of Vgr-1 and BMP-2a RNAs in embryonic, newborn, and adult tissues by in situ hybridization [3].

References