Local Administration of Ibandronate and Bone Morphogenetic Protein-2 After Ischemic Osteonecrosis of the Immature Femoral Head

Increased inflammatory responses is one of the major characteristics of osteonecrosis of the femoral head (ONFH). We aimed to investigate the function of bone morphogenetic protein 2 (BMP-2)/interleukin (IL)-34 axis in the inflammatory responses of ONFH. The systemic and local expression of BMPs in ONFH patients were detected by qRT-PCR and ELISA. In vitro osteoclast differentiation and ONFH mouse models, induced by 20 mg/kg methylprednisolone through intramuscular injection, were established using wild type and BMP-2-/- mice to explore the regulatory role of BMP-2 in pro-inflammatory responses and bone defects of ONFH. IL-34 expression and function were examined in vitro and in vivo through qRT-PCR, TRAP staining, and gene knockout. The systemic and local expression of BMPs were elevated in ONFH patients. BMP-2 reduced the production of pro-inflammatory cytokines and inhibited the differentiation of osteoclasts. Mechanistically, BMP-2 inhibited osteoclasts formation through suppressing IL-34 expression, and then promoted bone repair and alleviated ONFH. In conclusion, our study reveals that BMP-2 inhibits inflammatory responses and osteoclast formation through down-regulating IL-34.

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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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