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. 2019 Sep;35(9):550-558.
doi: 10.1002/kjm2.12095. Epub 2019 Jun 4.

HMGB1 promotes bone fracture healing through activation of ERK signaling pathway in a rat tibial fracture model

Ming-Qi Chen  1 , Jing-Jie Luan  1
Affiliations

HMGB1 promotes bone fracture healing through activation of ERK signaling pathway in a rat tibial fracture model

Ming-Qi Chen et al. Kaohsiung J Med Sci. 2019 Sep.

Abstract

This work was to investigate potential roles of HMGB1-mediated ERK pathway in the healing process of bone fracture. Rat tibial fracture models were established and divided into control (rats with normal saline), HMGB1 (rats with HMGB1), and HMGB1+ PD98059 groups (rats with HMGB1 and 1 mg/kg of ERK1/2 inhibitor PD98059) with 30 rats per each. The healing of rats' fracture was observed by X-ray films, the morphological changes of bone fractures by HE staining, the callus formation by micro-CT and biomechanical test, and the expression of osteogenesis-related genes, HMGB1 and ERK-related proteins by qRT-PCR and Western blot. Rats in the HMGB1 group was increased in X-ray scores, peak torque, torsional stiffness, and the bone volume fraction (bone volume/total volume, BV/TV); meanwhile, those rats presented elevations in osteogenesis-related genes and HMGB1 expressions, as well as p-ERK/ERK ratio. However, rats in the HMGB1+ PD98059 group was significantly reduced in X-ray score, peak torque, torsional stiffness, and BV/TV, as well as the expression of osteogenesis-related genes and the ratio of p-ERK/ERK, as compared to those from HMGB1 group. HMGB1 could promote the expressions of osteogenesis-related genes and accelerate the healing process of fracture via activation of the ERK signaling pathway.

Keywords: ERK pathway; HMGB1; bone callus; bone fracture.

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Conflict of interest statement

All authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The X‐ray film (A) and radiological scores (B) of rats' tibia in each group at 2, 3, 4 weeks after operation. Note: *P < .05 compared with the control group; #, P < .05 compared with the HMGB1 group
Figure 2
Figure 2
The morphological changes of fractures observed after HE staining (×100)
Figure 3
Figure 3
The peak torque and torsional stiffness of rats at 2, 3, 4 weeks after operation. Note: *, P < .05 compared with the control group; #, P < .05 compared with the HMGB1 group
Figure 4
Figure 4
The tibial fracture callus of rats in each group analyzed by micro‐CT scanning. Note: A, The micro‐CT scanning of fracture callus of rats in each group; B, the BV/TV ratio of rats in each group; *, P < .05 compared with the control group; #, P < .05 compared with HMGB1 group
Figure 5
Figure 5
The expression of osteogenesis‐related genes (Runx2, OCN, ALP, COL1A1A1, OSX, and Sox9) (A) and ERK, p38 and JNK‐pathway related proteins (B). Note: *, P < .05 compared with the control group; #, P < .05 compared with HMGB1 group
See this image and copyright information in PMC

References

    1. Singh V. Medicinal plants and bone healing. Natl J Maxillofac Surg. 2017;8(1):4–11. - PMC - PubMed
    1. Antapur P, Mahomed N, Gandhi R. Fractures in the elderly: When is hip replacement a necessity? Clin Interv Aging. 2011;6:1–7. - PMC - PubMed
    1. Ghiasi MS, Chen J, Vaziri A, Rodriguez EK, Nazarian A. Bone fracture healing in mechanobiological modeling: A review of principles and methods. Bone Rep. 2017;6:87–100. - PMC - PubMed
    1. Togral G, Arikan M, Korkusuz P, Hesar RH, Eksioglu MF. Positive effect of tadalafil, a phosphodiesterase‐5 inhibitor, on fracture healing in rat femur. Eklem Hastalik Cerrahisi. 2015;26(3):137–144. - PubMed
    1. Tzioupis C, Giannoudis PV. Prevalence of long‐bone non‐unions. Injury. 2007;38(suppl 2):S3–S9. - PubMed