Magnesium modification up-regulates the bioactivity of bone morphogenetic protein-2 upon calcium phosphate cement via enhanced BMP receptor recognition and Smad signaling pathway

Objective: We investigate the effects of bone morphogenetic protein-7 (BMP-7) on models with silica-induced and macrophage-mediated fibrosis and its possible mechanisms in vitro. Methods: Rat alveolar II epithelial (RLE-6TN) cells were incubated with the supernatant of mouse macrophage-like cells (RAW264.7) and treated with 0, 25, 50, and 100 μg/mL silica. Using Western blotting, the epithelial markers (surfactant proteins-C and E-cadherin) and the mesenchymal markers (fibronectin (FN) and viminten (Vim)) were detected. After neutralizing the BMP-7, the progress of fibrosis was assessed by the content of hydroxyproline (Hyp) and collagen I, III protein levels as well as the Smad signaling pathway proteins, including phosphorylated Smad1/5(P-Smad1/5) and phosphorylated Smad2/3(P-Smad2/3). Collagen I was also identified by immunofluorescence and pretreated with SB-431542, LDN-193189, or anti-BMP-7-neutralizing antibody. In addition, the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected using Western blotting. Results: The model of RLE-6TN cells was established successfully, the expressions of Vim, FN, MMP-2, and MMP-9 were upregulated, while the concentration of silica is increased. Neutralizing BMP-7 stimulated the decrease of P-Smad1/5 and the increase of P-Smad2/3, as well as the collagen I, collagen III, FN, and Hyp via Smad signaling pathway. Furthermore, pretreated with LDN-193189 or anti-BMP-7-neutralizing antibody, the expression of collagen I was increased, yet it was decreased with SB-431542 intervention. Conclusion: The activated BMP/Smad and suppressed transforming growth factor-β/Smad pathways could suppress silica-induced fibrosis via a MMP-dependent mechanism. BMP-7 is expected to be the optimized strategy of delaying the interstitial changes.

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Effects of strontium-modified calcium phosphate cement combined with bone morphogenetic protein-2 on osteoporotic bone defects healing in rats

Journal of Biomaterials Applications ◽

10.1177/0885328218765847 ◽

2018 ◽

Vol 33 (1) ◽

pp. 3-10 ◽

Cited By ~ 12

Author(s):

Zhoushan Tao ◽

Wanshu Zhou ◽

Yunyun Jiang ◽

Xingjin Wu ◽

Zhujun Xu ◽

...

Keyword(s):

Single Dose ◽

Calcium Phosphate ◽

Bone Formation ◽

Bone Morphogenetic Protein ◽

Calcium Phosphate Cement ◽

Bone Morphogenetic Protein 2 ◽

Local Administration ◽

Ovx Rats ◽

Local Bone ◽

Morphogenetic Protein

The objective of the present study was to incorporate strontium into calcium phosphate cement combined with a lower single-dose local administration of bone morphogenetic protein-2 to enhance its in vivo biodegradation and bone tissue growth. After the creation of a rodent critical-sized femoral metaphyseal bone defect, strontium-modified calcium phosphate cement was prepared by mixing sieved granules of calcium phosphate cement and 5% SrCO3 for medical use, and then strontium-modified calcium phosphate cement with dripped bone morphogenetic protein-2 solution (5 µg) was implanted into the defect of OVX rats until death at eight weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that a lower single-dose local administration of bone morphogenetic protein-2 combined local usage of strontium-modified calcium phosphate cement can increase the healing of defects in OVX rats. Furthermore, treatments with single-dose local administration of bone morphogenetic protein-2 and strontium-modified calcium phosphate cement showed a stronger effect on accelerating the local bone formation than calcium phosphate cement and strontium-modified calcium phosphate cement used alone. The results from our study demonstrate that combination of a lower single-dose local administration of bone morphogenetic protein-2 and strontium-modified calcium phosphate cement had an additive effect on local bone formation in osteoporosis rats.

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