Site-Specific Fracture Healing: Comparison between Diaphysis and Metaphysis in the Mouse Long Bone

Abstract

The process of fracture healing varies depending upon internal and external factors, such as the fracture site, mode of injury, and mechanical environment. This review focuses on site-specific fracture healing, particularly diaphyseal and metaphyseal healing in mouse long bones. Diaphyseal fractures heal by forming the periosteal and medullary callus, whereas metaphyseal fractures heal by forming the medullary callus. Bone healing in ovariectomized mice is accompanied by a decrease in the medullary callus formation both in the diaphysis and metaphysis. Administration of estrogen after fracture significantly recovers the decrease in diaphyseal healing but fails to recover the metaphyseal healing. Thus, the two bones show different osteogenic potentials after fracture in ovariectomized mice. This difference may be attributed to the heterogeneity of the skeletal stem cells (SSCs)/osteoblast progenitors of the two bones. The Hox genes that specify the patterning of the mammalian skeleton during embryogenesis are upregulated during the diaphyseal healing. Hox genes positively regulate the differentiation of osteoblasts from SSCs in vitro. During bone grafting, the SSCs in the donor’s bone express Hox with adaptability in the heterologous bone. These novel functions of the Hox genes are discussed herein with reference to the site-specificity of fracture healing.

Different cytokine expression profiles in metaphyseal and diaphyseal fracture healing may provide new insights in the field of bone regeneration

“…MCP-1 and TNF-α have been shown to do (23,24). The inflammatory phase of bone healing itself has been described to be limited, shorter and to terminate earlier in metaphyseal than diaphyseal fractures in animal models (22). This might explain our results in two ways, as they might be due to a similarly limited inflammatory phase in human fractures, as well as the fact that the inflammation might have been abrogated by the time samples were taken.…”

“…In contrast, inflammatory markers are "silenced" in patients with metaphyseal fractures. These observed differences between metaphyseal and diaphyseal fractures might be a result of their different mechanisms of MSC recruitment (22). As the metaphyseal region has more mesenchymal progenitors than the diaphyseal region, it might case that diaphyseal healing requires more pronounced cytokine signaling in order to regulate MSC recruitment and proliferation in the periosteum, as e.g.…”

Multifunctional Injectable Hydrogel Microparticles Loaded with miR‐29a Abundant BMSCs Derived Exosomes Enhanced Bone Regeneration by Regulating Osteogenesis and Angiogenesis

“…However, the release rates of Exos in 3.33%HB‐PEGDA@1.33%SH‐HA group reached nearly 80% (hyaluronidase) and 90% (H 2 O 2 ), respectively. Since the typical bone healing time for mice is ≈21–42 days, [ 27 ] 3.33%HB‐PEGDA@1.33%SH‐HA group was chosen for further experiments to ensure that HMPs can exert their maximum effect during the healing period. Interestingly, in PBS solution, minimal release of Exos was detected (Figure 3C Figure S9C,D, Supporting Information).…”

Development of a Metaphyseal Non-Union Model in the Osteoporotic Rat Femur

“…This emphasizes how vulnerable and concise the process of fracture healing is in rats with a depleted estrogen reservoir. Kolios et al reported that estrogen improves metaphyseal healing via an increase in the medullary callus formation in OVX rats [ 11 , 16 , 37 ]. In these experiments, OVX rats had a significant amount of cancellous bone in the metaphysis due to the oral-supplemented estrogen over a 10-week period before the injury.…”

“…Piezoelectric osteotomy generates micro-vibrations. Those allow for bone cutting, although the surrounding tissue, including the underlying soft and neurovascular tissue, is not damaged based upon the mechanical effect of ultrasound [ 37 , 38 , 39 , 40 ]. Specific to a piezoelectric osteotomy is the cavitation phenomenon.…”