Distinct Osteogenic Potentials of BMP-2 and FGF-2 in Extramedullary and Medullary Microenvironments

Nosho, Shuji; Tosa, Ikue; Ono, M.; Hara, Emilio Satoshi; Ishibashi, Keiichiro; Mikai, Akihiro; Tanaka, Yukimi; Kimura‐Ono, Aya; Komori, Taishi; Maekawa, Kenji; Kuboki, Takuo; Oohashi, Toshitaka

doi:10.3390/ijms21217967

Cited by 14 publications

(8 citation statements)

References 44 publications

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“…BMPs bind to ACVR1, which locates on the cell membrane surface phosphorylating SMAD1/5/9(8). Phosphorylated SMAD1/5/9(8) combine with SMAD4 and import into the nucleus, regulating transcription that drives endochondral ossification ( Nosho et al, 2020 ). When BMP receptors bonded with Activin A, SMAD2/3 is activated to regulate inflammation ( Rautela et al, 2019 ).…”

Section: Biological Mechanisms Of Homentioning

confidence: 99%

Heterotopic Ossification: Clinical Features, Basic Researches, and Mechanical Stimulations

Mei

et al. 2022

Front. Cell Dev. Biol.

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Heterotopic ossification (HO) is defined as the occurrence of extraskeletal bone in soft tissue. Although this pathological osteogenesis process involves the participation of osteoblasts and osteoclasts during the formation of bone structures, it differs from normal physiological osteogenesis in many features. In this article, the primary characteristics of heterotopic ossification are reviewed from both clinical and basic research perspectives, with a special highlight on the influence of mechanics on heterotopic ossification, which serves an important role in the prophylaxis and treatment of HO.

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Section: Biological Mechanisms Of Homentioning

confidence: 99%

Heterotopic Ossification: Clinical Features, Basic Researches, and Mechanical Stimulations

Mei

et al. 2022

Front. Cell Dev. Biol.

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“…Research shows that, the combination of BMP and FGF significantly enhanced osteogenesis than growth factor alone ( Gromolak et al, 2020 ; Hu et al, 2021 ). Bmp-2 may stimulate extramedullary bone regeneration, and FGF-2 may stimulate extramedullary bone regeneration ( Nosho et al, 2020 ). The combined use of BMP-2 and TGF-1 or TGF-3 showed stronger chondrogenic activity than BMP-2 alone ( Yu et al, 2010 ; Sang et al, 2014 ).…”

Section: Advanced Research Progress On the Biological Function Of Bmp...mentioning

confidence: 99%

Application of BMP in Bone Tissue Engineering

Zhu

Liu

Wang

et al. 2022

Front. Bioeng. Biotechnol.

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At present, bone nonunion and delayed union are still difficult problems in orthopaedics. Since the discovery of bone morphogenetic protein (BMP), it has been widely used in various studies due to its powerful role in promoting osteogenesis and chondrogenesis. Current results show that BMPs can promote healing of bone defects and reduce the occurrence of complications. However, the mechanism of BMP in vivo still needs to be explored, and application of BMP alone to a bone defect site cannot achieve good therapeutic effects. It is particularly important to modify implants to carry BMP to achieve slow and sustained release effects by taking advantage of the nature of the implant. This review aims to explain the mechanism of BMP action in vivo, its biological function, and how BMP can be applied to orthopaedic implants to effectively stimulate bone healing in the long term. Notably, implantation of a system that allows sustained release of BMP can provide an effective method to treat bone nonunion and delayed bone healing in the clinic.

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“…Over 20 subgroups of BMPs are known, among which, BMP‐2 is the primary subgroup that has been used in several in vitro and in vivo studies 2 . BMP‐2 is known to strongly induce osteogenesis and it plays an important role in the development and regeneration of bone and cartilage 3 . Based on animal experiments, Li et al 4 reported an improvement in osteogenesis when BMP‐2 and BMP‐7 were sequentially released compared with that when they were released separately.…”

Section: Introductionmentioning

confidence: 99%

“…2 BMP-2 is known to strongly induce osteogenesis and it plays an important role in the development and regeneration of bone and cartilage. 3 Based on animal experiments, Li et al 4 reported an improvement in osteogenesis when BMP-2 and…”

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confidence: 99%

Serial administration of rhBMP‐2 and alendronate enhances the differentiation of osteoblasts

et al. 2021

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Aim The incorporation of growth factors is an effective strategy to accelerate bone induction. Bone morphogenetic protein‐2 (BMP‐2) promotes osteoblast differentiation and induces bone formation. Alendronate (ALN) is an osteoclast deactivation drug. We investigated the effect of serial administration of recombinant human BMP‐2 (rhBMP‐2) and ALN on osteoblast differentiation. Methods The effect of serial administration of rhBMP‐2 (0‐150 ng/mL) and ALN (0‐15 µmol/L) on the viability and differentiation of a clonal murine calvarial cell line, MC3T3‐E1, was evaluated at various concentrations and for different periods. The Cell Counting Kit‐8 assay was used to assess cell viability. The alkaline phosphatase activity was evaluated as an indicator of osteogenic differentiation. The expression levels of runt domain‐containing transcription factor 2 (Runx2) and osteopontin (OPN) were analyzed by real‐time polymerase chain reaction and western blotting. Statistical analyses were performed using Student's t test. Results The serial treatment with rhBMP‐2 and ALN increased the expression of the differentiation‐related factors Runx2 and OPN, as well as the differentiation ability of osteoblasts compared with individual or simultaneous treatment. The osteoblasts treated with rhBMP‐2 followed by ALN showed the highest differentiation. The degree of differentiation in the group treated with rhBMP‐2 for 7 days followed by ALN for 3 days was increased by 1.5 times compared with that of the group treated with rhBMP‐2 alone (P < .01). Conclusion These findings indicate that the serial administration of rhBMP‐2 and ALN may exert osteogenic effects on osteoblastic cells via the upregulation of Runx2 and OPN.

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Distinct Osteogenic Potentials of BMP-2 and FGF-2 in Extramedullary and Medullary Microenvironments

Cited by 14 publications

References 44 publications

Heterotopic Ossification: Clinical Features, Basic Researches, and Mechanical Stimulations

Heterotopic Ossification: Clinical Features, Basic Researches, and Mechanical Stimulations

Application of BMP in Bone Tissue Engineering

Serial administration of rhBMP‐2 and alendronate enhances the differentiation of osteoblasts

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