Alteration of fracture stability influences chondrogenesis, osteogenesis and immigration of macrophages

Abstract

Mechanical conditions at the fracture line determine the mode of fracture healing (osteonal versus non-osteonal bone union). The aim of this study was to investigate the influence of differing degrees of fracture stability on the time course of chondrogenesis, enchondral ossification and immigration of macrophages into the fracture callus.Using a fracture model of the rat's tibia, histological (Azan staining), immunohistological (antibodies directed against the macrophage-specific surface antigen ED2), and molecular biological techniques (expression of the mRNA of the cartilage-specific collagen IX, osteocalcin -a marker for mature osteoblasts -and the macrophage-specific macrosialin) were employed.In terms of histology and molecular biology (collagen IX mRNA expression) chondrogenesis in the fracture gap continued for longer in less stable fractures. In more stable fractures bone formation -identified by osteocalcin mRNA expression -increased from day 12 onwards. The expression of the macrophage-specific surface antigen ED2 and the mRNA of macrosialin was more pronounced but of shorter duration in the more stable fractures.This study shows that differing degrees of fracture stability not only influence the interplay between osteogenesis and chondrogenesis but also alter the kinetics of macrophage immigration into the fracture callus. These findings could aid in better understanding the cytobiologic mechanisms of callus formation and may suggest that macrophages are an important factor not only in soft tissue healing but also in bone healing.

Unraveling macrophage contributions to bone repair

“…Circumstantial support for this hypothesis includes mRNA expression of macrophage macrosialin protein correlating with the expression of collagen IX in fractures. 30 In addition, colony stimulating factor-1 treatment over an extended time course (14 days) in rabbits resulted in a significantly increased mineralized callus area at 4 weeks post fracture, with no coincident increase in osteoclast or osteoblast number. 63 Macrophages were not assessed in this study, but given that they are a major colony stimulating factor-1 target it raises the possibility that either increased macrophage numbers or enhancement of a particular macrophage phenotype contributed to the observed increase in callus mineralization.…”

“…Data from animal models support the fact that macrophages are present within repair-associated tissues during this early anabolic phase with potentially sustained presence of robust numbers of macrophages during rigidly stabilized fixation compared with nonrigid repair scenarios. 12,29,30,50 During intramembranous ossification, macrophages were intercalated throughout areas of developing bone matrix, 12 whereas during endochondral repair they were excluded from the developing cartilage but were present in adjacent tissues. 29 Similarly, human fracture tissue studies support that, although macrophage numbers are higher in early fracture samples, they do persist in fractureassociated tissues and have been observed in association with Macrophages in bone repair AC Wu et al areas of bone formation.…”

“…29 These observations are somewhat paradoxical when compared with the wild-type setting, in which fewer infiltrating macrophages were associated with endochondral callus formation in nonrigid fracture repair models. 12,29,30,50 Hankemeier et al 30 similarly suggested that the magnitude of macrophage infiltration into the callus might influence the anabolic mechanism induced, but argued that fewer macrophages were indicative of nonrigid fracture repair via endochondral callus formation. We speculate that the magnitude of macrophage infiltration is secondary in importance to the type of macrophage being recruited/induced.…”

Fracture management in HIV positive individuals: a systematic review

“…HIV has also been shown to affect other chemical mediators, including interleukins 1 and 6 and tumour necrosis factor, which have been shown to play a role in the fracture repair process [8][9][10].…”

Interactions Between Multipotential Stromal Cells (MSCs) and Immune Cells During Bone Healing

“…In a mouse model of tibia fracture, both resident macrophages and inflammatory circulating macrophages were shown to be vital for the deposition of collagen type I (126). Furthermore, it has been shown that the gene expression of macrophage macrosialin protein is positively associated with the expression of collagen in fractures (127). In summary, macrophages are active during whole repair phase working synergistically with MSCs to help forming of collagen matrix and formation of new blood vessels.…”