Effects of leptin on femoral fracture in rats

Abstract

In this study, our objective was to evaluate effects of leptin on fracture healing in rats. Seventy two male Sprague-Dawley (SD) rats were randomized into 3 groups. Standardized femoral fractures were created in all the rats. Group A was treated with 1 mL normal saline (NS), group B with 0.3 μg/kg leptin in 1 mL NS, and group C with 0.5 μg/kg leptin in 1 mL NS for 2 weeks intraperitoneally. Each group was divided into three subgroups including 8 rats for evaluation at 2, 4 and 8 weeks. Radiological evaluation showed that callus formation of group B and C was all significantly higher than group A at 8 weeks (P=0.04 and P=0.013, respectively). There was no statistically significant difference in fracture healing between group B and group C at 8 weeks (P=0.197). Histological evaluation revealed fracture healing of group B and C was better than group A at 4 weeks (P=0.01 and P=0.002, respectively) and 8 weeks (P=0.008 and P=0.003, respectively). Micro-computed tomography (Micro-CT) analysis demonstrated that greater amounts of bony callus and evidence of bone fusion were observed in group B and C at 4 weeks (P=0.02 and P=0.04, respectively) and 8 weeks (P=0.005 and P=0.001, respectively) compared to group A. Group C also had better fracture healing than group B at 8 weeks (P=0.01). In conclusion, leptin has a positive effect on rat femoral fracture healing.

Keywords

fracture healing / leptin / rat / femoral fracture

References

[1] Thomas T. The complex effects of leptin on bone metabolism through multiple pathways[J]. Curr Opin Pharmacol, 2004, 4(3): 295–300

[2] Rodrigues L, Mouta R, Costa AR, Effects of high fat diet on salivary a-amylase, serum parameters and food consumption in rats[J]. Arch Oral Biol. 2015, 27; 60(6):854–862.

[3] Bertoni L, Ferretti M, Cavani F, Leptin increases growth of primary ossification centers in fetal mice[J]. J Anat, 2009, 215(5): 577–583

[4] Upadhyay J, Farr OM, Mantzoros CS. The role of leptin in regulating bone metabolism[J]. Metabolism, 2015, 64(1): 105–113

[5] Takeda S, Elefteriou F, Levasseur R, Leptin regulates bone formation via the sympathetic nervous system[J]. Cell, 2002, 111(3): 305–317

[6] Bertoni L, Ferretti M, Cavani F, Leptin increases growth of primary ossification centers in fetal mice[J]. J Anat, 2009, 215(5): 577–583

[7] Kume K, Satomura K, Nishisho S, Potential role of leptin in endochondral ossification[J]. J Histochem Cytochem, 2002, 50(2): 159–169

[8] Gaspar AP, Brandão CM, Lazaretti-Castro M. Bone mass and hormone analysis in patients with spinal cord injury: evidence for a gonadal axis disruption[J]. J Clin Endocrinol Metab, 2014, 99(12): 4649–4655

[9] Bonnet N, Gadois C, McCloskey E, Protective effect of beta blockers in postmenopausal women: influence on fractures, bone density, micro and macroarchitecture[J]. Bone, 2007, 40(5): 1209–1216

[10] Li J, Mori S, Kaji Y, Concentration of bisphosphonate (incadronate) in callus area and its effects on fracture healing in rats[J]. J Bone Miner Res, 2000, 15(10): 2042–2051

[11] Li J, Mori S, Kaji Y, Concentration of bisphosphonate (incadronate) in callus area and its effects on fracture healing in rats[J]. J Bone Miner Res, 2000, 15(10): 2042–2051

[12] Huo MH, Troiano NW, Pelker RR, The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats[J]. J Orthop Res, 1991, 9(3): 383–390

[13] Lane JM, Sandhu HS. Current approaches to experimental bone grafting[J]. Orthop Clin North Am, 1987, 18(2): 213–225

[14] Schindeler A, McDonald MM, Bokko P, Bone remodeling during fracture repair: The cellular picture[J]. Semin Cell Dev Biol, 2008, 19(5): 459–466

[15] Park AG, Paglia DN, Al-Zube L, Local insulin therapy affects fracture healing in a rat model[J]. J Orthop Res, 2013, 31(5): 776–782

[16] Mantzoros CS, Moschos S, Avramopoulos I, Leptin concentrations in relation to body mass index and the tumor necrosis factor-alpha system in humans[J]. J Clin Endocrinol Metab, 1997, 82(10): 3408–3413

[17] Mantzoros CS, Qu D, Frederich RC, Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice[J]. Diabetes, 1996, 45(7): 909–914

[18] Cadosch D, Gautschi OP, Thyer M, Humoral factors enhance fracture-healing and callus formation in patients with traumatic brain injury[J]. J Bone Joint Surg Am, 2009, 91(2): 282–288

[19] Zhang J, Li T, Xu L, Leptin promotes ossification through multiple ways of bone metabolism in osteoblast: a pilot study[J]. Gynecol Endocrinol, 2013, 29(8): 758–762

[20] Hamrick MW, Ferrari SL. Leptin and the sympathetic connection of fat to bone[J]. Osteoporos Int, 2008, 19(7): 905–912

[21] Bigford GE, Bracchi-Ricard VC, Nash MS, Alterations in mouse hypothalamic adipokine gene expression and leptin signaling following chronic spinal cord injury and with advanced age[J]. PLoS One, 2012, 7(7): e41073

[22] Brock JH, Rosenzweig ES, Blesch A, Local and remote growth factor effects after primate spinal cord injury[J]. J Neurosci, 2010, 30(29): 9728–9737

[23] Aloe L, Bianchi P, De Bellis A, Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury[J]. Neural Regen Res, 2014, 9(10): 1025–1030

[24] Wang L, Tang X, Zhang H, Elevated leptin expression in rat model of traumatic spinal cord injury and femoral fracture[J]. J Spinal Cord Med, 2011, 34(5): 501–509

[25] Turner RT, Kalra SP, Wong CP, Peripheral leptin regulates bone formation[J]. J Bone Miner Res, 2013, 28(1): 22–34

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