Bone morphogenetic protein–binding peptide reduces the inflammatory response to recombinant human bone morphogenetic protein-2 and recombinant human bone morphogenetic protein-7 in a rodent model of soft-tissue inflammation

Lee, Kwang-Bok; Murray, Samuel S.; Taghavi, Cyrus E.; Song, Kyung-Jin; Brochmann, Elsa J.; Johnson, Jared; Keorochana, Gun; Liao, Jen‐Chung; Wang, Jeffrey C.

doi:10.1016/j.spinee.2011.02.001

Cited by 35 publications

(27 citation statements)

References 29 publications

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“…Exogenous BMP2 has been demonstrated to induce bone formation, but adverse effects including ectopic bone formation, osteolysis, and seroma formation have been reported [11,12]. Soft tissue inflammation was seen as early as 3 hours after subcutaneous BMP2 implantation in a rat model, an effect dependent on BMP2 dose [39,40]. We previously reported that exogenous BMP2 induced pro-inflammatory interleukin production by osteoblast-like cells on microstructured Ti surfaces in a TAB/TAK-dependent manner [13].…”

Section: Discussionmentioning

confidence: 99%

Coordinated regulation of mesenchymal stem cell differentiation on microstructured titanium surfaces by endogenous bone morphogenetic proteins

Olivares-Navarrete¹,

Hyzy²,

Haithcock³

et al. 2015

Bone

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Human mesenchymal stem cells (MSCs) differentiate into osteoblasts on microstructured titanium (Ti) surfaces without addition of medium supplements, suggesting that surface-dependent endogenous mechanisms are involved. They produce bone morphogenetic proteins (BMPs), which regulate MSC differentiation and bone formation via autocrine/paracrine mechanisms that are modulated by changes in BMP mRNA and protein, receptors, and inhibitors (Noggin, Cerberus, Gremlin 1, and Chordin). We examined expression of BMPs, their receptors and their inhibitors over time and used BMP2-silenced cells to determine how modulating endogenous BMP signaling can affect the process. MSCs were cultured on tissue culture polystyrene or Ti [PT (Ra<0.4μm); sandblasted/acid-etched Ti (SLA, Ra=3.2μm); or hydrophilic-SLA (modSLA)]. BMP mRNAs and proteins increased by day 4 of culture. Exogenous BMP2 increased differentiation whereas differentiation was decreased in BMP2-silenced cells. Noggin was regulated by day 2 whereas Gremlin 1 and Cerberus were regulated after 6 days. Osteoblastic differentiation increased in cells cultured with blocking antibodies against Noggin, Gremlin 1, and Cerberus. Endogenous BMPs enhance an osteogenic microenvironment whereas exogenous BMPs are inhibitory. Antibody blocking of the BMP2 inhibitor Cerberus resulted in IL-6 and IL-8 levels that were similar to those observed when treating cells with exogenous BMP2, while antibodies targeting the inhibitors Gremlin or Noggin did not. These results suggest that microstructured titanium implants supporting therapeutic stem cells may be treated with appropriately selected agents antagonistic to extracellular BMP inhibitors in order to enhance BMP2 mediated bone repair while avoiding undesirable inflammatory side effects observed with exogenous BMP2 treatment.

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Section: Discussionmentioning

confidence: 99%

Coordinated regulation of mesenchymal stem cell differentiation on microstructured titanium surfaces by endogenous bone morphogenetic proteins

Olivares-Navarrete¹,

Hyzy²,

Haithcock³

et al. 2015

Bone

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“…However, other cytokines, such as IL-6, IL-1␤, and nitric oxide, are also secreted into inflammatory environments and may play different roles in osteogenesis (36 -39). Moreover, local inhibitors of inflammation such as triptolide and BMP-binding peptide, can enhance the osteoinductive efficacy of BMP-2 in vivo (40,41). However, direct evidence supporting an inhibitory effect of inflammation on BMP2-induced osteoblast differentiation is currently lacking.…”

Section: Discussionmentioning

confidence: 99%

Cyclic AMP Response Element-binding Protein H (CREBH) Mediates the Inhibitory Actions of Tumor Necrosis Factor α in Osteoblast Differentiation by Stimulating Smad1 Degradation

Jang

Jeong²,

Kim³

et al. 2015

Journal of Biological Chemistry

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Background: Severe inflammatory reactions delay wound healing of bone. Results: Tumor necrosis factor ␣ (TNF␣) inhibition of osteoblast differentiation is associated with increased cAMP response element-binding protein H (CREBH) and Smurf1 expression. Conclusion: CREBH mediates the inhibitory actions of TNF␣ in bone regeneration. Significance: CREBH is identified as a new mediator of inflammation-dependent bone degradation and a potential therapeutic target.

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“…However, it binds BMPs and TGF-b with high affinity and when added exogenously, inhibits the bone forming activities of these cytokines [9]. A synthetic peptide, the sequence of which is based on the BMP-binding domain of bovine Spp24, BMP binding peptide, has been reported to enhance BMP activity but also reduce softtissue inflammation caused by BMP-2 [20,21]. BMP binding peptide is hypothesized to bind to BMP and result in a ''slow release'' of BMP-2 or BMP-7 [22].…”

Section: Discussionmentioning

confidence: 99%

Secreted phosphoprotein 24 kD inhibits nerve root inflammation induced by bone morphogenetic protein-2

Tian

Scott³

et al. 2015

The Spine Journal

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Bone morphogenetic protein–binding peptide reduces the inflammatory response to recombinant human bone morphogenetic protein-2 and recombinant human bone morphogenetic protein-7 in a rodent model of soft-tissue inflammation

Cited by 35 publications

References 29 publications

Coordinated regulation of mesenchymal stem cell differentiation on microstructured titanium surfaces by endogenous bone morphogenetic proteins

Coordinated regulation of mesenchymal stem cell differentiation on microstructured titanium surfaces by endogenous bone morphogenetic proteins

Cyclic AMP Response Element-binding Protein H (CREBH) Mediates the Inhibitory Actions of Tumor Necrosis Factor α in Osteoblast Differentiation by Stimulating Smad1 Degradation

Secreted phosphoprotein 24 kD inhibits nerve root inflammation induced by bone morphogenetic protein-2

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