Bone morphogenetic protein-9 activates Smad and ERK pathways and supports human osteoclast function and survival in vitro

Bone Morphogenetic Proteins Signal Via SMAD and Mitogen-activated Protein (MAP) Kinase Pathways at Distinct Times during Osteoclastogenesis

“…Therefore, compensation by other TGF␤ superfamily signaling components is a plausible explanation for the continued activation of SMAD1/5/8 that we observe. Similar observations have been made in other systems; for example, a recent study has shown that shRNA knockdown of BMPRII interferes with ERK activation but not SMAD activation in mature osteoclasts (6). We further explored the signaling profile of differentiating WT osteoclasts in the presence and absence of BMP signaling.…”

“…TGF-␤ utilizes both AKT, through TAK1, and SMAD pathways to regulate cell survival in mature osteoclasts (5). BMPs also transduce their signals using the MAPK pathway in mature osteoclasts to promote resorption and cell survival (6), and BMPs have also been shown to activate MAPKs through TAK1 in chondrocytes (7,8). Several laboratories, including ours, have shown that osteoclasts express BMP receptors and respond directly to BMPs through activation of SMAD signaling (6, 9 -11).…”

Nanoscale Bioactive Glass Activates Osteoclastic Differentiation of RAW 264.7 Cells

“…Whereas RANKL stimulates several aspects of osteoclast function, OPG (osteoprotegerin) blocks RANKL, and inhibits bone resorption [25]. In in vitro studies, differentiation of different cell types into functioning osteoclast-like cells has been reported to occur upon cytokine stimulation [26][27][28]. Bioactive glasses are important biomaterials for bone tissue regeneration due to their bioactivity and osteoconductivity [15,16,27].…”

“…Bioactive glasses are important biomaterials for bone tissue regeneration due to their bioactivity and osteoconductivity [15,16,27]. Since the discovery of 45S5 BG in 1971 there have been over one million patients who have received this bone substitute for surgery [15,28] Rottensteiner et al [31]. Beside pastes and putties use, these hybrid systems are also promising approaches for additive manufacturing of biomedical implants and even for biofabrication [32,33].…”

Activin receptor-like kinase 1 as a target for anti-angiogenesis therapy

“…It has been shown that BMP-9 influences blood monocyte derived osteoclast survival by signalling through Smad1 and ERK/MAP kinase pathways, involving BMPRII and possibly ALK1. This leads to enhanced bone resorption and protects osteoclasts from apoptosis [73]. BMP-9 induces osteogenic differentiation of mesenchymal stem cells (MSCs), where both ALK1 and ALK2 signalling play a key role.…”