Granulocyte colony‐stimulating factor administration alters femoral biomechanical properties in C57BL/6 mice

Abstract

The clinical application of G-CSF is broadening. In addition to treating neutropenia and in bone marrow transplants, it is now being considered for functional recovery after myocardial infarction and stroke. It is thus very important that the effects of extended G-CSF administration on the skeleton are investigated. To simulate this potential clinical use of G-CSF in postmyocardial infarction or cerebral vascular accident, a 2-week course of administration was selected. Ten C57BL/6 mice at 22 weeks of age were given intraperitoneal injection of saline, and another nine of the same age were given G-CSF. Four weeks later, femurs were harvested and three-point-bend tests were performed until fracture. From the load-displacement curve recorded during the test, the stiffness, Young's modulus, fracture strength of the bone, fracture energy, and the total energy to break the femur were determined. The test data show that mice treated with G-CSF have significantly lower modulus in their femurs when compared to the controlled mice treated with saline. The stiffness demonstrates the largest decrease, by as much as 25%. As its clinical use increases, G-CSF effects on the mechanical properties of the skeleton become increasingly more important because many of these diseases occur in older patients with already compromised skeleton by osteopenia or osteoporosis. How G-CSF administration achieves these alterations in skeletal biomechanical properties is unclear. Although the current findings confirm its known temporary catabolic effects on bone homeostasis, it also suggests that a transient state of higher bone compliance following the end of G-CSF administration can be achieved that may have clinical benefits.

Bone marrow-derived cell mobilization by G-CSF to enhance osseointegration of bone substitute in high tibial osteotomy

“…Taken together, all these observations suggest that G-CSF may be safely administered and accelerate osseointegration and bone growth without reducing the bone density of the newly formed tissue. This seems in contrast with a previous work by Wu et al [60], suggesting a catabolic effect of G-CSF on bone homeostasis. It should be noted that the catabolic effects was temporary.…”

G‑CSF delays tooth extraction socket bone healing via the inhibition of bone turnover in mice

“…Microcomputed tomography analysis and bone morphometry of femurs and maxillae. Microcomputed tomography (µCT) scanning was performed to measure bone morphological indices of mouse femurs and maxillae as described previously (14). The femurs and maxillae in each group were harvested, stored in 70% ethanol at 4˚C, and analyzed using a micro (µ)-CT scanner (Scan Xmate-L090; Comscan Techno Co., Ltd.).…”

“…Silver-stained nucleolar organizer regions (AgNOR) staining was performed using a silver staining solution prepared by combining silver nitrate (2 volumes of 50% aqueous solution) (Wako Pure Chemical Industries, Ltd.) and formic acid (1 volume of 1% solution containing 2% gelatin) (14). The number of canaliculi per osteocyte lacuna (N.Ot.Ca/Ot.Lc.)…”

“…Soshi et al (13) reported that the bone mineral density of lumbar vertebrae and femora was significantly decreased in G-CSF-treated rats. Wu et al (14) investigated the effects of G-CSF administration on the skeleton. The test data show that mice treated with G-CSF have significantly lower stiffness, Young's modulus, and fracture strength of the bone in their femurs when compared with the controlled mice treated with saline.…”

How cell culture conditions affect the microstructure and nanomechanical properties of extracellular matrix formed by immortalized human mesenchymal stem cells: An experimental and modelling study

“…For elastic modulus, it has been reported that the modulus of collagen in nanoindentation ranges from 1.71 GPa to 3.31 GPa [45], the modulus of mouse femur is 10.76±1.61 GPa [46], and the modulus of human vertebral trabeculae is from 11.3 GPa to 15.8 GPa [47]. Thus, the elastic modulus of the matrix is similar to native bone after 7 to 14 days, and the relatively high Young's modulus of mineralized matrix in contrast to the collagen fibres indicates that the matrix is highly mineralized [45,48].…”