Intramembranous bone regeneration differs among common inbred mouse strains following marrow ablation

Abstract

Various intact and post-injury bone phenotypes are heritable traits. In this study, we sought to determine if intramembranous bone regeneration following marrow ablation differed among common inbred mouse strains and to identify how early the differences appear. We found a $four-fold difference in the regenerated bone volume 21 days after marrow ablation in females from four inbred mouse strains: FVB/N (15.7 AE 8.1%, mean and standard deviation), C3H/He (15.5 AE 4.2%), C57BL/6 (12.2 AE 5.2%), and BALB/c (4.0 AE 4.4%); with BALB/c different from FVB/N (p ¼ 0.007) and C3H/He (p ¼ 0.002). A second experiment showed that FVB/N compared to BALB/c mice had more regenerated bone 7 and 14 days after ablation (p < 0.001), while at 21 days FVB/N mice had a greater fraction of mineralizing surface (p ¼ 0.008) without a difference in mineral apposition rate. Thus, differences among strains are evident early during intramembranous bone regeneration following marrow ablation and appear to be associated with differences in osteogenic cell recruitment, but not osteoblast activity. The amount of regenerating bone was not correlated with other heritable traits such as the intact bone phenotype or soft tissue wound healing, suggesting that there may be independent genetic pathways for these traits. ß

Intramembranous bone regeneration and implant placement using mechanical femoral marrow ablation: rodent models

“…4 We showed that operated limbs exhibit bone formation within the ablated region as early as day 5 in the rat marrow ablation model and day 7 in the mouse marrow ablation model. 4,17 The newly formed intramedullary bone is resorbed and replaced by lamellar bone (that is, remodeled) beginning around day 10 post-ablation. Typically, the intramedullary contents return to baseline with few remaining trabeculae, if an implant has not been placed, between 28 and 56 days post-ablation.…”

“…4 The timing of these histological bone regeneration events is probably condensed in the rodent model compared to patients receiving joint replacements. 4,[41][42][43] The model has proven useful in understanding principles relevant to bone regeneration, 4,17 bone-implant contact 9,18,19 and implant fixation. 30 and bone ingrowth.…”

“…4,17,20,21,37,38 To assess the reproducibility of the model, we re-analyzed outcome data from the mouse marrow ablation model and the rat implant fixation model in which the animal strain, age, sex and experimental end points were comparable. Both mouse studies included females from FVB/NJ and BALB/cJ strains of the same age (10-11 weeks) with the same end point (bone volume/tissue volume, BV/TV) at 7 days post-marrow ablation.…”

“…14,15 Model choice depends upon the type of bone formation to be studied, as well as the importance of loadbearing, skeletal region and ability to translate to the clinic. The marrow ablation model is primarily used for two main purposes: (1) as a model for intramembranous bone regeneration 3,4,16,17 and (2) as a model to study implant fixation in orthopedics 9,[18][19][20][21] and dentistry. 22,23 Therefore, the model is of interest to orthopedic and dental research, including biomaterial specialists, implant designers and molecular biologists as well as the field of regenerative medicine.…”

Metaphyseal Fracture Healing

“…There can be a large variation in bone characteristics and fracture healing ability between different strains within a species [66,67] for example up to ten-fold differences in leucocyte numbers in the peripheral circulation of different mouse strains [68]. Membranous bone formation volume 21 days after marrow ablation can differ four-fold when comparing different strains within the mouse species [69].…”