The local cytokine and growth factor response to recombinant human bone morphogenetic protein-2 (rhBMP-2) after spinal fusion

Koerner, John D.; Markova, Dessislava; Schroeder, Greg D.; Calio, Brian; Shah, Anuj; Brooks, Corbin W.; Vaccaro, Alexander R.; Anderson, D. Greg; Kepler, Christopher K.

doi:10.1016/j.spinee.2018.03.006

Cited by 12 publications

(15 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…37 The BMP signalling pathway is mostly activated in fracture healing through endochondral ossification, indicating that this pathway could potentially regulate the mechanisms of healing in recruitment of skeletal progenitors. 38 Koerner et al 39 reported that fracture healing was a process in which multiple cytokines participate simultaneously. A variety of cytokines are known to determine the speed and quality of fracture healing, among which BMP is the most critical and BMP is present in the bone matrix and is the only local growth factor capable of independently inducing bone tissue formation.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-186 improves fracture healing through activating the bone morphogenetic protein signalling pathway by inhibiting SMAD6 in a mouse model of femoral fracture

Wang

2019

Bone & Joint Research

View full text Add to dashboard Cite

Objectives MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. Methods Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined. Results MicroRNA-186 was predicted to regulate SMAD6. Furthermore, SMAD6 was verified as a target gene of miR-186. Overexpressed miR-186 and SMAD6 silencing resulted in increased callus formation, BMD and BV/TV, as well as maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. In addition, the mRNA and protein levels of SMAD6 were decreased, while BMP-2 and BMP-7 levels were elevated in response to upregulated miR-186 and SMAD6 silencing. Conclusion In conclusion, the study indicated that miR-186 could activate the BMP signalling pathway to promote fracture healing by inhibiting SMAD6 in a mouse model of femoral fracture. Cite this article: Bone Joint Res 2019;8:550–562.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA-186 improves fracture healing through activating the bone morphogenetic protein signalling pathway by inhibiting SMAD6 in a mouse model of femoral fracture

Wang

2019

Bone & Joint Research

View full text Add to dashboard Cite

show abstract

“…Furthermore, growth factors, such as vascular endothelial growth factor, insulin-like growth factor 1, platelet-derived growth factor, and TGF-β, appeared to be repressed in the early stage of BMP2 treatment. This study showed that BMP2 leads to inflammatory reactions, but it may also contribute to enhancing the fusion process [131]. As in the study of Zhu et al (2017) [129], rats were approximately eight weeks in age, and spinal fusion was processed at the same level (L4-L5), but the rat subspecies was not the same.…”

Section: Bmps and Bmp Antagonists And Their Importance In Spinal Fusionmentioning

confidence: 78%

“…The study of Alden et al (1999) [130], which is based on the classic work of Urist et al (1965) [37], focused on viral gene therapy and observed paraspinal endochondral ossification after injections in the paraspinal musculature of gene constructs. However, in a recent study by Koerner et al (2018) [131], the application of BMP2 (10 or 100 µg) in a spinal fusion rat model demonstrated enhanced inflammatory reactions and inflammatory cytokine expression. Furthermore, growth factors, such as vascular endothelial growth factor, insulin-like growth factor 1, platelet-derived growth factor, and TGF-β, appeared to be repressed in the early stage of BMP2 treatment.…”

Section: Bmps and Bmp Antagonists And Their Importance In Spinal Fusionmentioning

confidence: 98%

“…Previous studies that investigated BMP2 particularly focused on spinal fusion models. Several in vivo rat studies have demonstrated the beneficial effect of BMP2 on bone healing and spinal fusion [129][130][131]. Zhu et al (2017) [129] showed early and large bone formation with transplanted DMBM and collagen binding BMP2 in a posterolateral rat spinal fusion model.…”

Section: Bmps and Bmp Antagonists And Their Importance In Spinal Fusionmentioning

confidence: 99%

See 1 more Smart Citation

Application of Cytokines of the Bone Morphogenetic Protein (BMP) Family in Spinal Fusion - Effects on the Bone, Intervertebral Disc and Mesenchymal Stromal Cells

May

Frauchiger

Albers

et al. 2019

CSCR

View full text Add to dashboard Cite

Low back pain is a prevalent socio-economic burden and is often associated with damaged or degenerated intervertebral discs (IVDs). When conservative therapy fails, removal of the IVD (discectomy), followed by intersomatic spinal fusion, is currently the standard practice in clinics. The remaining space is filled with an intersomatic device (cage) and with bone substitutes to achieve disc height compensation and bone fusion. As a complication, in up to 30% of cases, spinal non-fusions result in a painful pseudoarthrosis. Bone morphogenetic proteins (BMPs) have been clinically applied with varied outcomes. Several members of the BMP family, such as BMP2, BMP4, BMP6, BMP7, and BMP9, are known to induce osteogenesis. Questions remain on why hyper-physiological doses of BMPs do not show beneficial effects in certain patients. In this respect, BMP antagonists secreted by mesenchymal cells, which might interfere with or block the action of BMPs, have drawn research attention as possible targets for the enhancement of spinal fusion or the prevention of non-unions. Examples of these antagonists are noggin, gremlin1 and 2, chordin, follistatin, BMP3, and twisted gastrulation. In this review, we discuss current evidence of the osteogenic effects of several members of the BMP family on osteoblasts, IVD cells, and mesenchymal stromal cells. We consider in vitro and in vivo studies performed in human, mouse, rat, and rabbit related to BMP and BMP antagonists in the last two decades. We give insights into the effects that BMP have on the ossification of the spine. Furthermore, the benefits, pitfalls, and possible safety concerns using these cytokines for the improvement of spinal fusion are discussed.

show abstract

“…They also argued that the use of allografts in combination with BMP-2 did not achieve the full repair of defects [58]. Koerner et al showed that some adverse side effects of rhBMP-2 were increased inflammatory reactions and the expression of inflammatory cytokines [59]. When histological and immunohistochemical studies of BMP in the literature were examined, it was found that BMP was used with different growth factors and agents to prevent the side effects mentioned above.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the effects of bone morphogenetic protein-2 on the healing of bone calvarial defects in ovariectomized rats

Kadiroğlu¹,

Karayürek²,

Akbalık³

2020

Turk J Vet Anim Sci

View full text Add to dashboard Cite

Introduction Inadequate bone support for oral surgery and periodontal regeneration is a major problem for surgical applications. Additional graft materials are needed in dentistry to repair missing bone tissue. Currently, due to their osteogenic, osteoinductive, and osteoconductive effects, autogenous bone grafts are considered the gold standard under certain conditions [1]. However, other conditions, such as the presence of a second surgical site and the failure to obtain the desired amount of material, limit the use of autogenous bone grafts [2]. Because of this, many researchers have attempted to find an alternative to autografts. For instance, allografts have been used in dentistry for a long time. Allografts have osteoconductive and osteoinductive effects [3]. Regrettably, the devitalization process used to suppress the host immune response and prevent possible disease transmission in cadaveric allografts causes the loss of the mechanical, osteoinductive, and osteoconductive properties of the graft [4,5]. In addition, the maturation times of allografts are longer in defect regions than those of autografts [6,7]. Bone morphogenetic proteins (BMPs) are well known to induce osteogenic effects. Allografts typically contain BMPs that accelerate mesenchymal cell migration and attachment [3]. In both in vitro and in vivo studies of BMP-2, which is a type of BMP, the contribution of BMP-2 to ossification could be shown. BMP-2 promotes periodontal and bone regeneration in some animal models [8,9] and also induces differentiation of preosteoblast cells and thereby increases ossification [10,11]. Fundamentally, BMPs are types of growth factors and belong to the transforming growth factor (TGF-β) family [12]. There are variant BMPs that support bone regeneration, such as BMP-2,-4,-5,-6, and-7 [13]. Recombinant human bone morphogenetic protein-2 (rhBMP-2), generated by recombinant DNA technology from mammalian cells, is known to induce differentiation of osteoblasts at a cellular level and to induce osteogenesis in animal models [14]. Bone graft materials and osteoinductive agents have a synergistic effect [15]. The synergistic effect of BMPs and bone grafts on bone regeneration has been demonstrated in animal studies [11].

show abstract

The local cytokine and growth factor response to recombinant human bone morphogenetic protein-2 (rhBMP-2) after spinal fusion

Cited by 12 publications

References 18 publications

MicroRNA-186 improves fracture healing through activating the bone morphogenetic protein signalling pathway by inhibiting SMAD6 in a mouse model of femoral fracture

MicroRNA-186 improves fracture healing through activating the bone morphogenetic protein signalling pathway by inhibiting SMAD6 in a mouse model of femoral fracture

Application of Cytokines of the Bone Morphogenetic Protein (BMP) Family in Spinal Fusion - Effects on the Bone, Intervertebral Disc and Mesenchymal Stromal Cells

Evaluation of the effects of bone morphogenetic protein-2 on the healing of bone calvarial defects in ovariectomized rats

Contact Info

Product

Resources

About