Int J Biol Sci 2017; 13(10):1254-1265. doi:10.7150/ijbs.21258 This issue Cite

Research Paper

PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3

Hangang Chen1, 2, Xianding Sun2, Liangjun Yin1, Shuai Chen1, Ying Zhu2, Junlan Huang2, Wanling Jiang2, Bo Chen2, Ruobin Zhang2, Lin Chen2, Mao Nie1, Yangli Xie2✉, Zhongliang Deng1✉

1. Department of Orthopedic Surgery, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China;
2. Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

Citation:
Chen H, Sun X, Yin L, Chen S, Zhu Y, Huang J, Jiang W, Chen B, Zhang R, Chen L, Nie M, Xie Y, Deng Z. PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3. Int J Biol Sci 2017; 13(10):1254-1265. doi:10.7150/ijbs.21258. https://www.ijbs.com/v13p1254.htm
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Abstract

Graphic abstract

Bone fracture healing is processed through multiple stages including the cartilaginous callus formation and its transition to bony callus. FGFR3 negatively regulates chondrogenesis and enhances osteogenesis during skeleton development. We previously found in mice carrying gain-of-function mutation of FGFR3 that FGFR3 delays the healing of un-stabilized fracture that heals mainly through endochondral ossification. Since fracture is regularly treated in clinics with rigid fixation, and stabilized fracture is healed largely through intramembranous ossification, we asked whether FGFR3, a key regulator of osteogenesis, also affect the regeneration of stabilized fracture. We found that gain-of-function mutation of FGFR3 inhibits the initiation of chondrogenesis and the subsequent bone formation. We further studied whether PTH1-34 can improve the osteopenia and delayed healing of the stabilized tibia fracture in mice with achondroplasia. Fracture healing was evaluated by radiography, micro-CT, biomechanical tests, histology, and real-time polymerase chain reaction (RT-PCR) analysis. We found that PTH 1-34 can alleviate the decreased bone mass and compromised architecture in ACH mice. Histological analysis revealed that administration of PTH1-34 increased the size of both the total callus and cartilaginous callus at 14 days after the surgery in ACH mice. RT-PCR data suggested that systemic PTH1-34 accelerated the initiation of chondrogenesis and chondrocyte maturation (earlier and higher levels of expression of chondrogenesis related markers) and enhanced the osteogenic differentiation in the fracture callus in ACH mice. These results indicate that the PTH1-34 administration resulted in an enhanced callus formation during bone fracture healing in ACH mice, which is at least in part mediated by an increase of cartilaginous callus at early stage and the promotion of bone formation in bony callus. In summary, in this study we revealed that FGFR3 delays the regeneration of stabilized fracture by inhibiting both the chondrogenesis and osteogenesis, and PTH1-34 treatment can improve the dysregulated bone metabolism and delayed bone injury healing resulting from gain-of-function mutation of FGFR3.


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APA
Chen, H., Sun, X., Yin, L., Chen, S., Zhu, Y., Huang, J., Jiang, W., Chen, B., Zhang, R., Chen, L., Nie, M., Xie, Y., Deng, Z. (2017). PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3. International Journal of Biological Sciences, 13(10), 1254-1265. https://doi.org/10.7150/ijbs.21258.

ACS
Chen, H.; Sun, X.; Yin, L.; Chen, S.; Zhu, Y.; Huang, J.; Jiang, W.; Chen, B.; Zhang, R.; Chen, L.; Nie, M.; Xie, Y.; Deng, Z. PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3. Int. J. Biol. Sci. 2017, 13 (10), 1254-1265. DOI: 10.7150/ijbs.21258.

NLM
Chen H, Sun X, Yin L, Chen S, Zhu Y, Huang J, Jiang W, Chen B, Zhang R, Chen L, Nie M, Xie Y, Deng Z. PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3. Int J Biol Sci 2017; 13(10):1254-1265. doi:10.7150/ijbs.21258. https://www.ijbs.com/v13p1254.htm

CSE
Chen H, Sun X, Yin L, Chen S, Zhu Y, Huang J, Jiang W, Chen B, Zhang R, Chen L, Nie M, Xie Y, Deng Z. 2017. PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3. Int J Biol Sci. 13(10):1254-1265.

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