Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.727
Index Copernicus  – 166.39
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 2, February, p. 165–171

doi: 10.17219/acem/67755

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Splenectomy delays fracture healing by affecting the level of tumor necrosis factor alpha, interleukin 6 and bone morphogenetic protein

Wanan Xiao1,A,B,C,D, Xiaoxiao Yang1,B,C,D, Yang Wang1,B,C, Jianjun Li1,A,B,C,D,E,F

1 Department of Orthopedics, Shengjing Hospital of the China Medical University, Shenyang, China


Background. Abdominal injuries combined with bone fractures are increasing. Splenectomies are often required, but have prolonged healing time for bone fracture.
Objectives. The aim of the study was to explore the molecular mechanism for splenectomy delaying fracture healing.
Material and Methods. Eighty-four patients (42 received splenectomy) who received hip fractures operations were recruited in our hospital. One-year follow-up analysis was performed. To ensure the results, an animal model was established. Sprague-Dawley (SD) rats were randomly divided into 5 groups: group A: experimental group, femoral fractures + splenectomy; group B: femoral fractures; group C: splenectomy; group D: femoral fracture + sham splenectomy; group E: sham fracture. After the femoral fracture surgery, the callus status was evaluated by X-ray.
Results. After 1-year follow-up, the healing index and bone quality was higher in the fracture-operatedonly group than in the splenectomy group. In contrast, the rate of healing complications was lower in the fracture-operated-only group than in the splenectomy group. Biomarker analysis showed that the serum levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and bone morphogenetic protein (BMP) were higher in the fracture-operated-only group than in the splenectomy group. No difference of the callus status was found among the rats in groups B, D and E (p > 0.05), while there were significant differences of the callus status of the rats in groups A and C at different stages (p < 0.05). On the other hand, the levels of TNF-α, IL-6 and BMP increased, reached peak after 7-day splenectomy surgery, and then decreased significantly in groups A and C (p > 0.05).
Conclusion. Splenectomy delays fracture healing by affecting the levels of TNF-α, IL-6 and BMP.

Key words

immune function, splenectomy, fracture, tumor necrosis factor-alpha, bone morphogenetic protein

References (27)

  1. Liu S, Lei J, Zeng Z, Zhang Y. Management of traumatic splenic rupture in adults: A single center’s experience in Mainland China. Hepatogastroenterology. 2014;61:966–971.
  2. Yang GE, Duan X, Lin D, et al. Rapamycin-induced autophagy activity promotes bone fracture healing in rats. Exp Ther Med. 2015; 10:1327–1333.
  3. Histing T, Heerschop K, Klein M, et al. Characterization of the healing process in non-stabilized and stabilized femur fractures in mice. Arch Orthop Trauma Surg. 2016;136(2):203–211. doi:10.1007/s00402-015-2367-7
  4. Schmidt-Bleek K, Schell H, Lienau J, et al. Initial immune reaction and angiogenesis in bone healing. J Tissue Eng Regen Med. 2014;8: 120–130.
  5. Lin HN, Cottrell J, O’Connor JP. Variation in lipid mediator and cytokine levels during mouse femur fracture healing. J Orthop Res. 2016;34(11):1883–1893. doi:10.1002/jor.23213
  6. Fan H, Li TF, Gong N, Wang YX. Shanzhiside methylester, the principle effective iridoid glycoside from the analgesic herb Lamiophlomis rotata, reduces neuropathic pain by stimulating spinal microglial beta-endorphin expression. Neuropharmacology. 2016;101:98–109.
  7. TNF-alpha accelerates bone fracture healing. Bonekey Rep. 2012; 1:100.
  8. Uliana GN, Tambara EM, Baretta GA. Use of remifentanil to reduce propofol injection pain and the required propofol dose in upper digestive tract endoscopy diagnostic tests. Braz J Anesthesiol. 2015;65:437–444.
  9. Farzandipour M, Sheikhtaheri A. Evaluation of factors influencing accuracy of principal procedure coding based on ICD-9-CM: An Iranian study. Perspect Health Inf Manag. 2009;6:5.
  10. Williams CA, Hauser KW, Correia JA, Frias JL. Ascertainment of gastroschisis using the ICD-9-CM surgical procedure code. Birth Defects Res A Clin Mol Teratol. 2005;73:646–648.
  11. Singh M, Nagrath AR, Maini PS. Changes in trabecular pattern of the upper end of the femur as an index of osteoporosis. J Bone Joint Surg Am. 1970;52:457–467.
  12. Bookout AL, Mangelsdorf DJ. Quantitative real-time PCR protocol for analysis of nuclear receptor signaling pathways. Nucl Recept Signal. 2003;1:e012.
  13. Karakantza M, Theodorou GL, Mouzaki A, Theodori E, Vagianos C, Maniatis A. In vitro study of the long-term effects of post-traumatic splenectomy on cellular immunity. Scand J Immunol. 2004;59: 209–219.
  14. Kimpel D, Dayton T, Fuseler J, et al. Splenectomy attenuates streptococcal cell wall-induced arthritis and alters leukocyte activation. Arthritis Rheum. 2003;48:3557–3567.
  15. Lieberman JR, Daluiski A, Einhorn TA. The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am. 2002;84-A(6):1032–1044.
  16. Goldring SR, Gravallese EM. Mechanisms of bone loss in inflammatory arthritis: Diagnosis and therapeutic implications. Arthritis Res. 2000;2:33–37.
  17. Nanes MS. Tumor necrosis factor-alpha: Molecular and cellular mechanisms in skeletal pathology. Gene. 2003;321:1–15.
  18. Hou CH, Hou SM, Tang CH. Ultrasound increased BMP-2 expression via PI3K, Akt, c-Fos/c-Jun, and AP-1 pathways in cultured osteoblasts. J Cell Biochem. 2009;106:7–15.
  19. Lu Z, Wang G, Dunstan CR, et al. Activation and promotion of adipose stem cells by tumour necrosis factor-alpha preconditioning for bone regeneration. J Cell Physiol. 2013;228:1737–1744.
  20. Dai Q, Qi X, Guo M. Interleukin 6 (IL-6) and bone resorption. Chin J Orthop. 1996;16:516–516.
  21. Tanaka Y, Nakayamada S, Okada Y. Osteoblasts and osteoclasts in bone remodeling and inflammation. Curr Drug Targets Inflamm Allergy. 2005;4:325–328.
  22. Itoh S, Udagawa N, Takahashi N, et al. A critical role for interleukin 6 family-mediated Stat3 activation in osteoblast differentiation and bone formation. Bone. 2006;39:505–512.
  23. Hughes FJ, Howells GL. Interleukin 6 inhibits bone formation in vitro. Bone Miner. 1993;21:21–28.
  24. Chae HJ, Ha KC, Lee GY, et al. Interleukin 6 and cyclic AMP stimulate release of cathepsin B in human osteoblasts. Immunopharmacol Immunotoxicol. 2007;29:155–172.
  25. Cho TJ, Kim JA, Chung CY, et al. Expression and role of interleukin 6 in distraction osteogenesis. Calcif Tissue Int. 2007;80:192–200.
  26. Kuroda S, Virdi AS, Dai Y, Shott S, Sumner DR. Patterns and localization of gene expression during intramembranous bone regeneration in the rat femoral marrow ablation model. Calcif Tissue Int. 2005;77:212–225.
  27. Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn TA. Fracture healing as a post-natal developmental process: Molecular, spatial, and temporal aspects of its regulation. J Cell Biochem. 2003;88:873–884.