BMP3: To Be or Not To Be a BMP

Bahamonde, Matthew E.; Lyons, Karen M.

doi:10.2106/00004623-200100001-00008

Cited by 93 publications

(98 citation statements)

References 24 publications

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“…21 Others view BMP-3 as a negative regulator of osteogenesis. 22,23 Our results demonstrated that the gene expression of BMP-3 and the closely related BMP-3B were lower in nonunions compared to standard healing fractures, and suggested the downregulation of BMP-3 and 3B were implicated in nonunion formation.…”

Section: Discussionmentioning

confidence: 66%

Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures

2006

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Nonunion is a challenging problem that may occur following certain bone fractures. However, there has been little investigation of the molecular basis of nonunions. Bone morphogenetic proteins (BMPs) play a significant role in osteogenesis. However, little is known about the expression patterns of BMPs in abnormal bone healing that results in nonunion formation. These facts prompted us to investigate and compare the gene expression patterns of BMPs and their antagonists in standard healing fractures and nonunions using rat experimental models. Standard closed healing fractures and experimental atrophic nonunions produced by periosteal cauterization at the fracture site were created in rat femurs. At postfracture days 3, 7, 10, 14, 21, and 28, total RNA was extracted from the callus of standard healing fracture and fibrous tissue of nonunion (n ¼ 4 per each time point and each group). Gene expression of BMPs, BMP antagonists, and other regulatory molecules were studied by methods including Genechip 1 microarray and real-time quantitative RT-PCR. Gene expression of BMP-2, 3, 3B, 4, 6, 7, GDF-5, 7, and BMP antagonists noggin, drm, screlostin, and BAMBI were significantly lower in nonunions compared to standard healing fractures at several time points. Downregulation in expression of osteogenic BMPs may account for the nonunions of fracture. The balance between BMPs and their endogenous antagonists is critical for optimal fracture healing. ß

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Section: Discussionmentioning

confidence: 66%

Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures

2006

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“…52 When C2C12 cells transduced by AdBMP-3 and one of the four osteogenic AdBMPs were coinjected intramuscularly for 3 weeks, BMP-2 and BMP-6-induced ossification was completely blocked by BMP-3, and most of the BMP-7-induced ossification was inhibited by BMP-3 ( Figure 4a). However, BMP-3 coinjection did not exert any effect on BMP-9-induced calcification (Figure 4a), strongly suggesting that BMP-9 may exert its osteogenic activity via a distinct signaling mechanism.…”

Section: Antagonistic Effect Of Bmp-3 On Bmp-induced Bone Formationmentioning

confidence: 99%

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

et al. 2004

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Efficacious bone regeneration could revolutionize the clinical management of bone and musculoskeletal disorders. Although several bone morphogenetic proteins (BMPs) (mostly BMP-2 and BMP-7) have been shown to induce bone formation, it is unclear whether the currently used BMPs represent the most osteogenic ones. Until recently, comprehensive analysis of osteogenic activity of all BMPs has been hampered by the fact that recombinant proteins are either not biologically active or not available for all BMPs. In this study, we used recombinant adenoviruses expressing the 14 types of BMPs (AdBMPs), and demonstrated that, in addition to currently used BMP-2 and BMP-7, BMP-6 and BMP-9 effectively induced orthotopic ossification when either AdBMP-transduced osteoblast progenitors or the viral vectors were injected into the quadriceps of athymic mice. Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points. BMP-3, a negative regulator of bone formation, was shown to effectively inhibit orthotopic ossification induced by BMP-2, BMP-6, and BMP-7. However, BMP-3 exerted no inhibitory effect on BMP-9-induced bone formation, suggesting that BMP-9 may transduce osteogenic signaling differently. Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration.

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“…In fact, despite their name, not all members of the BMP family are directly involved in skeletogenesis; they display distinct spatio-temporal expression patterns, with consequent diversified roles in the morphogenesis of even non-skeletal structures during embryo development (H. Cheng et al, 2003;Dudley et al, 1995;Jena et al, 1997;Luo et al, 1995;Mcpherron et al, 1999;Solloway et al, 1998;Zhao et al, 1996). BMP2, BMP4 and BMP7 (also known as osteogenic protein-1, OP-1, see Figure 1) are the most extensively studied osteogenic BMPs, being involved in basic skeletal body patterning mechanisms (Bahamonde et al, 2001;Gimble et al, 1995;Ozkainak et al, 1990). In vitro, BMP-2, BMP-4, and BMP-7 can induce the differentiation of multipotent mesenchymal cells into both osteochondrogenic lineage cells and osteoblast precursor cells, suggesting their essential contribute to both direct and indirect ossification mechanisms occurring in vertebrates (Balint et al, 2003;Canalis et al, 2003;Yamaguchi et al, 2000).…”

Section: Bone Morphogenetic Proteins (Bmps)mentioning

confidence: 99%

“…As an alternative mechanism, BMP2 can also bind to preformed heteromeric receptor complexes and activate a Smad-independent transduction cascade, which results in the induction of alkaline phosphatase activity via p38-mitogen-activated protein kinase (MAPK; Kozawa et al, 2002;Guicheux et al, 2003;Nohe et al, 2002). BMP3 (osteogenin) appears to antagonize the osteogenic effects of BMP2 in stromal cells, likely acting via an activin-mediated pathway (Bahamonde et al, 2001). …”

Section: Bmp Receptors and Intracellular Signal Transductionmentioning

confidence: 99%