11β‑hydroxysteroid dehydrogenases as targets in the treatment of steroid‑associated femoral head necrosis using antler extract

Pu,Ribusurong; Peng,Hao

doi:10.3892/etm.2017.5459

11β‑hydroxysteroid dehydrogenases as targets in the treatment of steroid‑associated femoral head necrosis using antler extract

Authors:
- Ribusurong Pu
- Hao Peng
View Affiliations

Affiliations: Orthopaedics Department, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China, Orthopaedics Department, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: November 7, 2017 https://doi.org/10.3892/etm.2017.5459
Pages: 977-984

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the therapeutic effect of deer antler extract on avascular necrosis of the femoral head (ANFH) induced by steroids, and to confirm that 11β‑hydroxysteroid dehydrogenases (11β‑HSD) are one of the targets of treatment with antler extract. A total of 30 rabbits were randomly divided into 5 groups (n=6): A control, ANFH, ANFH + antler (250 mg/kg), ANFH + antler (500 mg/kg) and ANFH + antler (1,000 mg/kg) group. Rabbits in the experimental groups were injected with methylprednisolone and horse serum to establish a steroid‑induced ANFH (SANFH) model. Rabbits in the ANFH + antler (250 mg/kg), ANFH + antler (500 mg/kg) and ANFH + antler (1,000 mg/kg) groups were treated with intraperitoneal injection of 250, 500 or 1,000 mg/kg antler extract/day, respectively, for 60 days. Serum samples were then extracted to determine total cholesterol (CT) and triglyceride levels, treat osteoblasts, measure 11β‑HSD (11β‑HSD1) and 11β‑HSD2 and alkaline phosphatase (ALP) levels and cellular apoptosis, and determine the proportion of osteoblasts in each phase of the cell cycle. Serum CT and triglyceride levels in SANFH rabbits significantly decreased as the concentration of antler increased (P<0.05). 11β‑HSD1 levels in the femoral heads of SANFH rabbits and osteoblasts following treatment with antler‑containing serum decreased as the concentration of antler used increased, whereas levels of 11β‑HSD1 increased significantly (P<0.05). The proliferation of osteoblasts and ALP levels in osteoblasts increased as the antler concentration increased, whereas the number of osteoblasts in the G0/G1 phase decreased significantly (P<0.05). The current study demonstrated that treatment with antler extract has a therapeutic effect on ANFH induced by steroids in rabbits and may regulate the expression of 11β‑HSD in femoral heads and osteoblasts, as well as promoting the proliferation of osteoblasts.

View Figures

View References

1	Rodriguez-Merchan EC, Martinez-Lloreda A, Sanjurjo MJ and Jimenez-Yuste V: Osteonecrosis of the femoral headMusculoskeletal Aspects of Haemophilia. Rodriguez-Merchan EC, Goddard NJ and Lee CA: Springer; Berlin, Heidelberg: pp. 153–158. 2014
2	Liakakos T, Thomakos N, Fine PM, Dervenis C and Young RL: Peritoneal adhesions: Etiology, pathophysiology and clinical significance. recent advances in prevention and management. Dig Surg. 18:260–273. 2001. View Article : Google Scholar : PubMed/NCBI
3	Fisher DE and Bickel WH: Corticosteroid-induced avascular necrosis. a clinical study of seventy-seven patients. J Bone Joint Surg Am. 53:859–873. 1971. View Article : Google Scholar : PubMed/NCBI
4	Bozic KJ, Zurakowski D and Thornhill TS: Survivorship analysis of hips treated with core decompression for nontraumatic osteonecrosis of the femoral head. J Bone Joint Surg Am. 81:200–209. 1999. View Article : Google Scholar : PubMed/NCBI
5	Zaidi M, Sun L, Robinson LJ, Tourkova IL, Liu L, Wang Y, Zhu LL, Liu X, Li J, Peng Y, et al: ACTH protects against glucocorticoid-induced osteonecrosis of bone. Proc Natl Acad Sci USA. 107:pp. 8782–8787. 2010; View Article : Google Scholar : PubMed/NCBI
6	Su P, Li R, Liu S, Zhou Y, Wang X, Patil N, Mow CS, Mason JC, Huang D and Wang Y: Age at onset-dependent presentations of premature hip osteoarthritis, avascular necrosis of the femoral head, or legg-calvé-perthes disease in a single family, consequent upon a p. Gly1170Ser mutation of COL2A1. Arthritis Rheum. 58:1701–1706. 2008. View Article : Google Scholar : PubMed/NCBI
7	Liu J, Chen H, Zhang H, et al: Clinical characteristics and risk factors of avascular necrosis of the femoral head in patients with lupus nephritis. Chin J Nephrol Dial Transplant. 2013.
8	Zeng C, Song YC, Cai DZ and Liu B: Clinical characteristics and complication prevention of total hip arthroplasty for the patients of femoral head necrosis with systemic lupus erythematosus. Chin J Joint Surg. 454–458. 2009.(In Chinese).
9	Kawate K, Yajima H, Ohgushi H, Kotobuki N, Sugimoto K, Ohmura T, Kobata Y, Shigematsu K, Kawamura K, Tamai K and Takakura Y: Tissue-engineered approach for the treatment of steroid-induced osteonecrosis of the femoral head: Transplantation of autologous mesenchymal stem cells cultured with beta-tricalcium phosphate ceramics and free vascularized fibula. Artif Organs. 30:960–962. 2006. View Article : Google Scholar : PubMed/NCBI
10	Zhao FC, Li ZR and Guo KJ: Clinical analysis of osteonecrosis of the femoral head induced by steroids. Orthop Surg. 4:28–34. 2012. View Article : Google Scholar : PubMed/NCBI
11	LaPorte DM, Mont MA, Mohan V, Jones LC and Hungerford DS: Multifocal osteonecrosis. J Rheumatol. 25:1968–1974. 1998.PubMed/NCBI
12	Barnes PJ and Adcock IM: How do corticosteroids work in asthma? Ann Intern Med. 139:359–370. 2003. View Article : Google Scholar : PubMed/NCBI
13	Liu X, Zhang Y and Huo L: A study on application of protocol nursing in corticosteroids treatment compliance of nephritic syndrome patients. Chin Nurs Res. 45:539–545. 2008.
14	Lee AC and Wong LG: Facial palsy, corticosteroids, and acute leukemia. Pediatr Neurol. 36:137–138. 2007. View Article : Google Scholar : PubMed/NCBI
15	Steelman J and Kappy M: Adrenal suppression and growth retardation from ocular corticosteroids. J Pediatr Ophthalmol Strabismus. 38:177–178. 2001.PubMed/NCBI
16	Morton NM: Obesity and corticosteroids: 11beta-hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease. Mol Cell Endocrinol. 316:154–164. 2010. View Article : Google Scholar : PubMed/NCBI
17	Need AG: Corticosteroids and osteoporosis. Aust N Z J Med. 17:267–272. 1987. View Article : Google Scholar : PubMed/NCBI
18	Hengge UR, Ruzicka T, Schwartz RA and Cork MJ: Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 54:1–18. 2006. View Article : Google Scholar : PubMed/NCBI
19	Gebhard KL and Maibach HI: Relationship between systemic corticosteroids and osteonecrosis. Am J Clin Dermatol. 2:377–388. 2001. View Article : Google Scholar : PubMed/NCBI
20	Skalka HW and Prchal JT: Effect of corticosteroids on cataract formation. Arch Ophthalmol. 98:1773–1777. 1980. View Article : Google Scholar : PubMed/NCBI
21	Lavin PJ and Workman R: Cushing syndrome induced by serial occipital nerve blocks containing corticosteroids. Headache. 41:902–904. 2001. View Article : Google Scholar : PubMed/NCBI
22	Cranney A, Welch V, Adachi J, Homik J, Shea B, Suarez-Almazor ME, Tugwell P and Wells GA: Calcitonin for preventing and treating corticosteroid-induced osteoporosis (Review). Cochrane Database Syst Rev. CD0019832000.PubMed/NCBI
23	Kerachian MA, Cournoyer D, Harvey EJ, Chow TY, Bégin LR, Nahal A and Séguin C: New insights into the pathogenesis of glucocorticoid-induced avascular necrosis: Microarray analysis of gene expression in a rat model. Arthritis Res Ther. 12:R1242010. View Article : Google Scholar : PubMed/NCBI
24	Baktursun P, Peng H and Li BB: Effects of antler powder on treatment of corticosteroid-induced avascular necrosis of the femoral head in rats. J Clin Rehabilitative Tiss Eng Res. 346:1030–1031. 2011.
25	Tian L, Tian XY, Fan NN, Liang XP and YU XM: Treatment of avascular necrosis of the femoral head (ANFH) with induced differentiation VEGF-165 gene modified mesenchymal stem cells in rabbits. Journal of Shenyang Medical College. 1–144. 2009.
26	Sen RK: Management of avascular necrosis of femoral head at pre-collapse stage. Indian J Orthop. 43:6–16. 2009. View Article : Google Scholar : PubMed/NCBI
27	Pritchett JW: Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin Orthop Relat Res. 1–178. 2001.
28	Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT and Lin RM: The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. J Bone Joint Surg Am. 87:2155–2159. 2005. View Article : Google Scholar : PubMed/NCBI
29	Kruuk EB, Slate J, Pemberton JM, Brotherstone S, Guinness F and Clutton-Brock T: Antler size in red deer: Heritability and selection but no evolution. Evolution. 56:1683–1695. 2002. View Article : Google Scholar : PubMed/NCBI
30	Gould SJ: The origin and function of ‘BIZARRE’ structures: Antler size and skull size in the ‘IRISHELK,’ megaloceros giganteus. Evolution. 28:191–220. 1974. View Article : Google Scholar : PubMed/NCBI
31	Chapman DI: Antler structure and function-a hypothesis. J Biomech. 14:195–197. 1981. View Article : Google Scholar : PubMed/NCBI
32	Li Y, Zhao Y, Tang R and Qu X: Preventive and therapeutic effects of antler collagen on osteoporosis in ovariectomized rats. Afr J Biotechnol. 9:6437–6441. 2010.
33	Baktursun P, Peng H and Li BB: Effects of antler powder on treatment of corticosteroid-induced avascular necrosis of the femoral head in rats[J]. Journal of Clinical Rehabilitative Tissue Engineering Research. 346:1030–1031. 2011.
34	Seckl JR and Walker BR: Minireview: 11beta-hydroxysteroid dehydrogenase type 1-a tissue-specific amplifier of glucocorticoid action. Endocrinology. 142:1371–1376. 2001. View Article : Google Scholar : PubMed/NCBI
35	Nakano D and Nishiyama A: Programmed 11β-hydroxysteroid dehydrogenase type 2 reduction: A possible cause of adult-onset disease? J hypertens. 29:201–203. 2011. View Article : Google Scholar : PubMed/NCBI
36	Kaur K, Hardy R, Ahasan MM, Eijken M, van Leeuwen JP, Filer A, Thomas AM, Raza K, Buckley CD, Stewart PM, et al: Synergistic induction of local glucocorticoid generation by inflammatory cytokines and glucocorticoids: Implications for inflammation associated bone loss. Ann Rheum Dis. 69:1185–1190. 2010. View Article : Google Scholar : PubMed/NCBI
37	Kerachian MA, Séguin C and Harvey EJ: Glucocorticoids in osteonecrosis of the femoral head: A new understanding of the mechanisms of action. J Steroid Biochem Mol Biol. 114:121–128. 2009. View Article : Google Scholar : PubMed/NCBI
38	Combes R and Balls M: Comments on the sub-group reports of the EU technical expert working group on the revision of directive 86/609/EEC on the protection of animals used for experimental and other scientific purposes. Altern Lab Anim. 35:155–175. 2007.PubMed/NCBI
39	Wen Q, Ma L, Chen YP, Yang L, Luo W and Wang XN: A rabbit model of hormone-induced early avascular necrosis of the femoral head. Biomed Environ Sci. 21:398–403. 2008. View Article : Google Scholar : PubMed/NCBI
40	Mont MA, Jones LC, Einhorn TA, Hungerford DS and Reddi AH: Osteonecrosis of the femoral head. Potential treatment with growth and differentiation factors. Clin Orthop Relat Res. 355 Suppl:S314–S335. 1998. View Article : Google Scholar : PubMed/NCBI
41	Baneux PJ, Garner D, Mcintyre HB and Holshuh HJ: Euthanasia of rabbits by intravenous administration of ketamine. J Am Vet Med Assoc. 189:1038–1039. 1986.PubMed/NCBI
42	Glenn EM: Steroids, nonsteroids, intermediary metabolism, inflammation and their probable interrelationships. Hormonal Steroids Biochem Pharmacol Ther. 1:319–349. 1964. View Article : Google Scholar
43	Hemphill N and Morgan DR: Speaker: For inflammation, steroids should be used boldly. Primary Care Optometry News. April. 2013, https://www.healio.com/footer/healio-dot-com/about-the-wyanoke-group
44	Denso P: Free communications-session 1-inflammation & steroidsfree. Clin Experiment Aller. 23:75–76. 1993. View Article : Google Scholar
45	Griffith JF, Antonio GE, Kumta SM, Hui DS, Wong JK, Joynt GM, Wu AK, Cheung AY, Chiu KH, Chan KM, et al: Osteonecrosis of hip and knee in patients with severe acute respiratory syndrome treated with steroids. Radiology. 235:168–175. 2005. View Article : Google Scholar : PubMed/NCBI
46	Chen RC, Tang XP, Tan SY, Liang BL, Wan ZY, Fang JQ and Zhong N: Treatment of severe acute respiratory syndrome with glucosteroids: The guangzhou experience. Chest. 129:1441–1452. 2006. View Article : Google Scholar : PubMed/NCBI
47	Rapała K, Walczak P and Truszczyńska A: Orthopedic diagnostic and therapeutic problems in avascular poststeroid necrosis of femur head in the course acute lymphoblastic leukemia-description of 3 cases. Chir Narzadow Ruchu Ortop Pol. 75:121–125. 2010.PubMed/NCBI
48	Wu D, Song D, Ni J and Dai R: Avascular necrosis of the femoral head due to the bilateral injection of heroin into the femoral vein: A case report. Exp Ther Med. 6:1041–1043. 2013. View Article : Google Scholar : PubMed/NCBI
49	Iwata H, Hasegawa Y, Mizuno M, Genda E, Kataoka Y and Kada A: Progression of avascular necrosis of femoral head and choice of treatment. Nagoya J Med Sc. 54:27–39. 1992.
50	Jones LC and Hungerford DS: Osteonecrosis: Etiology, diagnosis, and treatment. Curr Opin Rheumatol. 16:443–449. 2004. View Article : Google Scholar : PubMed/NCBI
51	Hungerford DS: Treatment of osteonecrosis of the femoral head: Everything's new. J Arthroplasty. 22 4 Suppl 1:S91–S94. 2007. View Article : Google Scholar
52	Fritsch EW and Gleitz M: Ceramic femoral head fractures in total hip arthroplasty. Clin Orthop Relat Res. 1–136. 1996.PubMed/NCBI
53	Cabanela ME: The bipolar prosthesis in avascular necrosis of the femoral head. Semin Arthroplasty. 2:228–233. 1991.PubMed/NCBI
54	Kawai K, Tamaki A and Hirohata K: Steroid-induced accumulation of lipid in the osteocytes of the rabbit femoral head. A histochemical and electron microscopic study. J Bone Joint Surg Am. 67:755–763. 1985. View Article : Google Scholar : PubMed/NCBI
55	Jones JP Jr: Fat embolism and osteonecrosis. Orthop Clin North Am. 16:595–633. 1985.PubMed/NCBI
56	Jones JP Jr and Sakovich L: Fat embolism of bone. A roentgenographic and histological investigation, with use of intra-arterial lipiodol, in rabbits. J Bone Joint Surg Am. 48:149–164. 1966. View Article : Google Scholar : PubMed/NCBI
57	Cooper MS, Walker EA, Bland R, Fraser WD, Hewison M and Stewart PM: Expression and functional consequences of 11beta-hydroxysteroid dehydrogenase activity in human bone. Bone. 27:375–381. 2000. View Article : Google Scholar : PubMed/NCBI
58	Cooper MS, Rabbitt EH, Goddard PE, Bartlett WA, Hewison M and Stewart PM: Osteoblastic 11beta-hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid exposure. J Bone Miner Res. 17:979–986. 2002. View Article : Google Scholar : PubMed/NCBI
59	Chen XP, Qian H, Wu JJ, Ma XW, Gu ZX, Sun HY, Duan YZ and Jin ZL: Expression of vascular endothelial growth factor in cultured human dental follicle cells and its biological roles. Acta Pharmacol Sin. 28:985–993. 2007. View Article : Google Scholar : PubMed/NCBI