CORRELATION BETWEEN LOCAL MICROENVIRONMENT LEPTIN EXPRESSION AND AVASCULAR NECROSIS OF THE FEMORAL HEAD_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LIU Tie , SU Qingjun , ZANG Lei , KANG Nan , WANG Yu , HAI Yong.

Department of Orthopaedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, P.R.China. Corresponding author: HAI Yong, E-mail: spinesurgeon@163.com;

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Keywords：

Avascular necrosis of the femoral head; Leptin; Fat metabolism; Bone metabolism

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Objective To discuss the correlation between the letpin level and the pathogenesis of avascular necrosis of the femoral head (ANFH) by measuring the leptin expression of the femoral head in patients with ANFH. Methods Between July 2009 and February 2011, 16 patients with ANFH (including 10 cases of steroid-induced ANFH and 6 cases of alcohol-induced ANFH, ANFH group) and 11 patients with proximal femur fracture (control group) were included in the experiment. There was no significant difference in age, weight, and body mass index between 2 groups (P gt; 0.05). The peripheral blood and bone marrow were extracted to measure the blood lipid level and the free fat (FF) content, respectively. ELISA was used to detect the levels of the leptin, soluble leptin receptor (sLR), osteoprotegerin (OPG), and soluble receptor activator of nuclear factor κB (sRANKL); the leptin biological activity and the activity of osteoclasts were calculated. The femoral head specimens were harvested to count leptin-positive cells by immunohistochemical staining. Results No significant difference in the blood lipid level was found between 2 groups (P gt; 0.05), but the FF content in ANFH group was significantly lower than that in control group (t= — 14.230, P=0.000). The intramedullary leptin expression was found in both groups; however, the intramedullary leptin level in ANFH group decreased significantly when compared with the level in control group (t=4.425, P=0.002). There were significant differences in the levels of leptin, OPG, and sRANKL between 2 groups (P lt; 0.05). The leptin biological activity of ANFH group was significantly lower than that of control group (P lt; 0.05), but the activity of osteoclasts of ANFH group was significantly higher than that of control group (P lt; 0.05). There was a positive correlation between the leptin level and leptin biological activity (r=0.922 7, P=0.000 0), and a negative correlation between the leptin level and OPG content (r= — 0.396 2, P=0.040 8), FF content (r= — 0.806 1, P=0.000 0), while it had no correlation between the leptin level and sLR and sRANKL content (P gt; 0.05). Conclusion Intramedullary expression and bioactivity of the leptin decrease significantly in ANFH patients, which may play an important role in the pathogenesis of ANFH.

Citation： LIU Tie,SU Qingjun,ZANG Lei,KANG Nan,WANG Yu,HAI Yong.. CORRELATION BETWEEN LOCAL MICROENVIRONMENT LEPTIN EXPRESSION AND AVASCULAR NECROSIS OF THE FEMORAL HEAD. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(11): 1319-1323. doi: Copy

1.	Jones LC, Hungerford DS. The pathogenesis of osteonecrosis. Instr Course Lect, 2007, 56: 179-196.
2.	Hernigou P, Beaujean F. Abnormalities in the bone marrow of the iliac crest in patients who have osteonecrosis secondary to corticosteroid therapy or alcohol abuse. J Bone Joint Surg (Am), 1997, 79(7): 1047-1053.
3.	Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284(5411): 143-147.
4.	Zipori D. The stem state: mesenchymal plasticity as a paradigm. Curr Stem Cell Res Ther, 2006, 1(1): 95-102.
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8.	Martin RB, Chow BD, Lucas PA. Bone marrow fat content in relation to bone remodeling and serum chemistry in intact and ovariectomized dogs. Calcif Tissue Int, 1990, 46(3): 189-194.
9.	Tang CH, Lu DY, Yang RS, et al. Leptin-induced IL-6 production is mediated by leptin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, Akt, NF-kappaB, and p300 pathway in microglia. J Immunol, 2007, 179(2): 1292-1302.
10.	Nuttall ME, Gimble JM. Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications. Curr Opin Pharmacol, 2004, 4(3): 290-294.
11.	Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell, 2000, 100(2): 197-207.
12.	Astudillo P, Rios S, Pastenes L, et al. Increased adipogenesis of osteoporotic human-mesenchymal stem cells (MSCs) characterizes by impaired leptin action. J Cell Biochem, 2008, 103(4): 1054-1065.
13.	Mohanty ST, Kottam L, Gambardella A, et al. Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis. Arthritis Res Ther, 2010, 12(4): R149.
14.	Thomas T, Gori F, Khosla S, et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology, 1999, 140(4): 1630-1638.
15.	Maddalozzo GF, Turner RT, Edwards CH, et al. Alcohol alters whole body composition, inhibits bone formation, and increases bone marrow adiposity in rats. Osteoporos Int, 2009, 20(9): 1529-1538.
16.	Huang L, Wang Z, Li C. Modulation of circulating leptin levels by its soluble receptor. J Biol Chem, 2001, 276(9): 6343-6349.
17.	Oh SR, Sul OJ, Kim YY, et al. Saturated fatty acids enhance osteoclast survival. J Lipid Res, 2010, 51(5): 892-899.
18.	Reid IR. Fat and bone. Arch Biochem Biophys, 2010, 503(1): 20-27.
19.	Scheller EL, Song J, Dishowitz MI, et al. Leptin functions peripherally to regulate differentiation of mesenchymal progenitor cells. Stem Cells, 2010, 28(6): 1071-1080.
20.	Hozumi A, Osaki M, Goto H, et al. Bone marrow adipocytes support dexamethasone-induced osteoclast differentiation. Biochem Biophys Res Commun, 2009, 382(4): 780-784.
21.	Chang JK, Ho ML, Yeh CH, et al. Osteogenic gene expression decreases in stromal cells of patients with osteonecrosis. Clin Orthop Relat Res, 2006, (453): 286-292.
22.	Wang BL, Sun W, Shi ZC, et al. Decreased proliferation of mesenchymal stem cells in corticosteroid-induced osteonecrosis of femoral head. Orthopedics, 2008, 31(5): 444.

1. Jones LC, Hungerford DS. The pathogenesis of osteonecrosis. Instr Course Lect, 2007, 56: 179-196.
2. Hernigou P, Beaujean F. Abnormalities in the bone marrow of the iliac crest in patients who have osteonecrosis secondary to corticosteroid therapy or alcohol abuse. J Bone Joint Surg (Am), 1997, 79(7): 1047-1053.
3. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284(5411): 143-147.
4. Zipori D. The stem state: mesenchymal plasticity as a paradigm. Curr Stem Cell Res Ther, 2006, 1(1): 95-102.
5. McCarty DJ, Koopmann WJ. Arthritis and allied conditions: a textbook of rheumatology. 12th eds. Philadelphia: Lea & Febiger, 1993: 1677-1695.
6. Kitajima M, Shigematsu M, Ogawa K, et al. Effects of glucocorticoid on adipocyte size in human bone marrow. Med Mol Morphol, 2007, 40(3): 150-156.
7. Sugano N, Kubo T, Takaoka K, et al. Diagnostic criteria for non-traumatic osteonecrosis of the femoral head. A multicentre study. J Bone Joint Surg (Br), 1999, 81(4): 590-595.
8. Martin RB, Chow BD, Lucas PA. Bone marrow fat content in relation to bone remodeling and serum chemistry in intact and ovariectomized dogs. Calcif Tissue Int, 1990, 46(3): 189-194.
9. Tang CH, Lu DY, Yang RS, et al. Leptin-induced IL-6 production is mediated by leptin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, Akt, NF-kappaB, and p300 pathway in microglia. J Immunol, 2007, 179(2): 1292-1302.
10. Nuttall ME, Gimble JM. Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications. Curr Opin Pharmacol, 2004, 4(3): 290-294.
11. Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell, 2000, 100(2): 197-207.
12. Astudillo P, Rios S, Pastenes L, et al. Increased adipogenesis of osteoporotic human-mesenchymal stem cells (MSCs) characterizes by impaired leptin action. J Cell Biochem, 2008, 103(4): 1054-1065.
13. Mohanty ST, Kottam L, Gambardella A, et al. Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis. Arthritis Res Ther, 2010, 12(4): R149.
14. Thomas T, Gori F, Khosla S, et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology, 1999, 140(4): 1630-1638.
15. Maddalozzo GF, Turner RT, Edwards CH, et al. Alcohol alters whole body composition, inhibits bone formation, and increases bone marrow adiposity in rats. Osteoporos Int, 2009, 20(9): 1529-1538.
16. Huang L, Wang Z, Li C. Modulation of circulating leptin levels by its soluble receptor. J Biol Chem, 2001, 276(9): 6343-6349.
17. Oh SR, Sul OJ, Kim YY, et al. Saturated fatty acids enhance osteoclast survival. J Lipid Res, 2010, 51(5): 892-899.
18. Reid IR. Fat and bone. Arch Biochem Biophys, 2010, 503(1): 20-27.
19. Scheller EL, Song J, Dishowitz MI, et al. Leptin functions peripherally to regulate differentiation of mesenchymal progenitor cells. Stem Cells, 2010, 28(6): 1071-1080.
20. Hozumi A, Osaki M, Goto H, et al. Bone marrow adipocytes support dexamethasone-induced osteoclast differentiation. Biochem Biophys Res Commun, 2009, 382(4): 780-784.
21. Chang JK, Ho ML, Yeh CH, et al. Osteogenic gene expression decreases in stromal cells of patients with osteonecrosis. Clin Orthop Relat Res, 2006, (453): 286-292.
22. Wang BL, Sun W, Shi ZC, et al. Decreased proliferation of mesenchymal stem cells in corticosteroid-induced osteonecrosis of femoral head. Orthopedics, 2008, 31(5): 444.

Chinese Journal of Reparative and Reconstructive Surgery

CORRELATION BETWEEN LOCAL MICROENVIRONMENT LEPTIN EXPRESSION AND AVASCULAR NECROSIS OF THE FEMORAL HEAD

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