Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation.

Ogawa, Yasushi; Schmidt, Daiana; Nathan, Ranga M.; Armstrong, R. M.; Miller, Kathleen L.; Sawamura, Steven J.; Ziman, Jill M.; Erickson, Karen L.; Leon, Elena Rueda de; Rosen, David

doi:10.1016/s0021-9258(19)49702-0

Cited by 112 publications

(6 citation statements)

References 16 publications

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“…Thus the various factors that influence the ossification process may be contained in the bone matrix carrier and the crude BMP. 19,20 Currently, the mechanisms that determine the pathway of ossification are not well known. However, our data indicate that the role of rhBMP-2 in an extraskeletal site is to enhance the differentiation into the osteoblasts from the mesenchymal cells.…”

Section: Discussionmentioning

confidence: 99%

The role of recombinant human bone morphogenetic protein-2 in PLGA capsules at an extraskeletal site of the rat

Isobe

Yamazaki

Mori

et al. 1999

J. Biomed. Mater. Res.

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Bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor-beta (TGF-beta) superfamily and has strong bone-inductive activity in vivo. To examine the role of BMP-2 in an extraskeletal site of rat using a controlled release system of peptides, we encapsulated the recombinant human BMP-2 (rhBMP-2) with poly(DL-lactide-co-glycolide) (PLGA) and implanted the rhBMP-2/PLGA capsules in the subcutaneous area of rats. Upon histochemical examination, it was found that bone-inducing cells having alkaline phosphatase (ALP) activity appeared around the capsules by the suitably released rhBMP-2. In addition, the temporal histological examination showed that direct bone formation without cartilage occurred in the process of this ectopic bone induction. These data indicate that the role of rhBMP-2 in the extraskeletal site of rats is to induce the differentiation of mesenchymal cells into the osteoblasts.

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Section: Discussionmentioning

confidence: 99%

The role of recombinant human bone morphogenetic protein-2 in PLGA capsules at an extraskeletal site of the rat

Isobe

Yamazaki

Mori

et al. 1999

J. Biomed. Mater. Res.

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“…Although activin-A is known to be abundantly localized in bone matrix, neither activin-B nor activin-AB have been detected in bone. 17 Recent studies reported that the role of activin-A in bone metabolism, however conflicting evidence exists concerning the role of activin-A in bone formation and destruction. 18,19 Activin-A exerts stimulatory effects on several hematopoietic cell lineages that are responsible for the differentiation of osteoclasts and it has also been reported to inhibit and stimulate osteoclastogenesis in vitro 20,21 ; however, the mechanisms underlying the effects of activin-A on osteoclast formation and function are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Structurally, activins are homo‐ or heterodimeric proteins containing two disulfide‐linked βA and/or βB subunits result in formation of activin‐A (βAβA), activin‐AB (βAβB), or activin‐B (βBβB). Although activin‐A is known to be abundantly localized in bone matrix, neither activin‐B nor activin‐AB have been detected in bone …”

Section: Introductionmentioning

confidence: 99%

Mechanisms involved in enhancement of osteoclast formation by activin‐A

Kajita

Ariyoshi

Okinaga

et al. 2018

J of Cellular Biochemistry

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Several growth factors in bone tissues are reported to be associated with osteoclastogenesis. Activin-A, a member of the transforming growth factor-β (TGF-β) family is known to be present in bone tissues and an important regulator in osteoclastogenesis with SMAD-mediated signaling being crucial for inducing osteoclast differentiation. In the present study, we examined the effect and underlying mechanisms of activin-A on osteoclast formation in vitro culture systems. Activin-A enhanced osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW 264.7 cells induced by receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) and/or macrophage stimulating factor (M-CSF). We also found that activin-A stimulated bone resorption and actin ring formation induced by RANKL and/or M-CSF. Furthermore, activin-A enhanced RANKL-induced expression of nuclear factor of activated T cell cytoplasmic 1 (NFATc1), a key regulator of osteoclastogenesis, thereby increasing osteoclastogenesis-related marker gene expression, including tartrate-resistant acid phosphatase, osteoclast stimulatory transmembrane protein, and cathepsin K. Blockage of receptor binding by follistatin, an activing-binding protein suppressed the activin-A-mediated stimulation of NFATc1. In addition, activin-A increased RANKL-induced c-fos expression without significantly affecting the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathway. Pre-treatment of the cells with a specific inhibitor of SMAD2/3 attenuated the activin-A-induced expression of NFATc1 and co-immunoprecipitation assay revealed that treatment with activin-A increased physical interaction of phosphorylated-c-fos and phosphorylated-SMAD2 protein induced by RANKL. These results suggest that activin-A enhances RANKL-induced osteoclast formation mediated by interaction of c-fos and smad2/3.

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“…Inhibins are composed of heterodimers of one et chain and one 13 chain (13A or 13a chains). Activins are dimers of 13 chains; a homodimer of 13A chains is denoted activin A. Activins are multifunctional proteins; they stimulate mesoderm induction in Xenopus embryos (Smith et al, 1990; van den Eijnden-Van Raaij et al, 1990;Asashima et al, 1990;Thomsen et al, 1990), stimulate the differentiation of erythroid progenitor cells (Murata et al, 1988;, and modulate the bone formation by BMP (Ogawa et al, 1992).…”

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confidence: 99%

Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects.

Yamashita

Dijke

Huylebroeck

et al. 1995

The Journal of Cell Biology

461

258

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Abstract. Proteins in the TGF-[~ superfamily transduce their effects through binding to type I and type II serine/threonine kinase receptors. Osteogenic protein-1 (OP-1, also known as bone morphogenetic protein-7 or BMP-7), a member of the TGF-[3 superfamily which belongs to the BMP subfamily, was found to bind activin receptor type I (ActR-I), and BMP receptors type IA (BMPR-IA) and type IB (BMPR-IB) in the presence of activin receptors type II (ActR-II) and type liB (ActR-IIB). The binding affinity of OP-1 to ActR-II was two-to threefold lower than that of activin A. A transcriptional activation signal was transduced after binding of OP-1 to the complex of ActR-I and ActR-II, or that of BMPR-IB and ActR-II. These results indicate that ActR-II can act as a functional type II receptor for OP-1, as well as for activins. Some of the known biological effects of activin were observed for OP-1, including growth inhibition and erythroid differentiation induction. Compared to activin, OP-1 was shown to be a poor inducer of mesoderm in Xenopus embryos.Moreover, follistatin, an inhibitor of activins, was found to inhibit the effects of OP-1, if added at a 10-fold excess. However, certain effects of activin, like induction of follicle stimulating hormone secretion in rat pituitary cells were not observed for OP-1. OP-1 has overlapping binding specificities with activins, and shares certain but not all of the functional effects of activins. Thus, OP-1 may have broader effects in vivo than hitherto recognized.

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Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation.

Cited by 112 publications

References 16 publications

The role of recombinant human bone morphogenetic protein-2 in PLGA capsules at an extraskeletal site of the rat

The role of recombinant human bone morphogenetic protein-2 in PLGA capsules at an extraskeletal site of the rat

Mechanisms involved in enhancement of osteoclast formation by activin‐A

Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects.

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