Pigs are useful for the molecular study of bone inflammation and regeneration in humans

Abstract

Pigs are used with increased frequency to model different kinds of orthopedic surgical conditions. In order to show the full potential of porcine models in orthopedic research, it is therefore required to examine the expression of bone regulatory genes in pigs affected by orthopedic surgery and compare it to the expression in humans and mice as mice, are one of the most applied animal species in orthopedics today. In the present study, the local molecular response to drilling of a tibial implant cavity, and the subsequent insertion of a steel implant was examined in a porcine model. Pigs were euthanized five days after drilling of the bone. The molecular response of 73 different genes was analyzed using a high-throughput quantitative polymerase chain reaction platform and compared to histopathology. Histologically, it was found that bone remodeling was initiated on day 5 after surgery and was associated with upregulation of several genes involved in bone degradation and formation ( CTSK, ACP5, IBSP, RANK, RANKL and COL1A1). Interleukin-6 and several acute-phase proteins (C3, SAA and ITIH4) were significantly upregulated, indicating their importance in the initial process of healing and osseointegration. All tested bone morphogenic proteins (BMP2, -4 and -7) including their inhibitor noggin were also significantly upregulated. Surprisingly, vascular endothelial growth factor A was not found to be regulated five days after surgery while several other vascular growth factors (ANGPT1, ANGPT2 and PTN) were upregulated. The pig was found to be a useful model for elucidation of bone regulatory genes in humans.

Implant‐associated osteomyelitis: Development, characterisation, and application of a porcine model

“…Furthermore, bone remodelling and cortical bone mineralization rates in pigs and humans are similar [43,44,46]. Finally, a recent study on the porcine IAO model inoculated with saline demonstrated that the local expression pattern of inflammatory and bone regulatory genes in bone tissue exposed to surgery was similar to that reported in human studies [10].…”

“…In saline-inoculated animals, the surgical inoculation procedure per se resulted in thermal bone necrosis and debris around the implant cavity (Fig. 12B; II, III) [10]. In addition, a small amount of inflammatory cellular infiltration occurred.…”

“…During the past 5 years, the porcine IAO model has been applied in several studies [10][11][12][13]. In brief, the model was used as the basis of an EU HORIZON 2020 Research and Innovation Programme project (Novel Marine Biomolecules Against Biofilm [NoMoRFilm] no.…”

Microdialysis for the Assessment of Intervertebral Disc and Vertebral Cancellous Bone Metabolism in a Large Porcine Model

“…Induction of general anaesthesia is known to cause physiological alterations that may have affected the local tissue metabolism. Although pigs have been shown to resemble humans in terms of physiology, anatomy and bone inflammation and regeneration (30)(31)(32)(33), the porcine intervertebral disc and vertebral cancellous bone differ from that of humans in several ways (15).…”

Towards in silico Models of the Inflammatory Response in Bone Fracture Healing

“…While nonhuman primates are the most representative model of the human immune system ( Wagar et al, 2018 ), pigs and sheep are normally used to model bone repair since their bone anatomy, mineral composition, regeneration capacity and biomechanical properties are relatively similar to human’s ( Sparks et al, 2020 ). Moreover, compared to mice, their immune system is closer to the human one ( Lüthje et al, 2018 ). As a consequence, pigs and sheep are the first choices as large animal models of the inflammatory response in bone fracture healing.…”