• 首都醫(yī)科大學(xué)附屬北京朝陽醫(yī)院骨科（北京，100020）;

目的 探討股骨頭缺血性壞死（avascular necrosis of the femoral head，ANFH）患者骨髓瘦素與局部微環(huán)境骨、脂代謝指標(biāo)相關(guān)性。 方法實(shí)驗(yàn)標(biāo)本均由2009年7月－2011年2月收治患者自愿捐贈(zèng)，其中ANFH患者16例（ANFH組），其中激素性10例，酒精性6例；股骨上段骨折或創(chuàng)傷性骨性關(guān)節(jié)炎患者11例（對(duì)照組）。兩組年齡、體重及體重指數(shù)比較，差異均無統(tǒng)計(jì)學(xué)意義（P  gt; 0.05），具有可比性。取兩組患者外周血檢測(cè)血脂水平；術(shù)中抽取骨髓測(cè)量髓內(nèi)脂肪組織（free fat，F(xiàn)F）含量，ELISA檢測(cè)瘦素、可溶性瘦素受體（soluble leptin receptor，sLR）、骨保護(hù)素（osteoprotegerin，OPG）及可溶性NF-κB受體活化因子配基（soluble receptor activator of NF-κB，sRANKL）濃度，計(jì)算瘦素生物學(xué)活性及破骨細(xì)胞活性。取股骨頭標(biāo)本行免疫組織化學(xué)染色，計(jì)算瘦素陽性表達(dá)細(xì)胞百分率。 結(jié)果兩組外周血標(biāo)本血脂水平比較，差異均無統(tǒng)計(jì)學(xué)意義（P  gt; 0.05）；但ANFH組骨髓FF含量顯著低于對(duì)照組（t= —14.230，P=0.000）。兩組標(biāo)本骨細(xì)胞及骨髓基質(zhì)細(xì)胞中均有瘦素表達(dá)，但ANFH組瘦素陽性表達(dá)細(xì)胞百分率顯著低于對(duì)照組（t=4.425，P=0.002）。ELISA檢測(cè)示，除sLR外，兩組骨髓瘦素、OPG、sRANKL含量比較，差異均有統(tǒng)計(jì)學(xué)意義（P  lt; 0.05）。ANFH組瘦素生物學(xué)活性顯著低于對(duì)照組，破骨細(xì)胞活性高于對(duì)照組，差異均有統(tǒng)計(jì)學(xué)意義（P  lt; 0.05）。在所有患者中，髓內(nèi)瘦素水平與瘦素生物學(xué)活性成正相關(guān)（r=0.922 7，P=0.000 0），與OPG含量成負(fù)相關(guān)（r= —0.396 2，P=0.040 8），與骨髓FF含量成負(fù)相關(guān)（r= — 0.806 1，P=0.000 0），與sLR、sRANKL無相關(guān)性（P  gt; 0.05）。 結(jié)論ANFH患者股骨頭髓內(nèi)瘦素表達(dá)及其生物學(xué)活性均較正常股骨頭顯著降低，瘦素作用不足可能是ANFH發(fā)病的一個(gè)重要原因，其變化與髓內(nèi)骨、脂代謝變化相關(guān)。

引用本文： 劉鐵,蘇慶軍,藏磊,康南,王宇,海涌. 股骨頭缺血性壞死與局部微環(huán)境瘦素表達(dá)的相關(guān)性研究. 中國修復(fù)重建外科雜志, 2012, 26(11): 1319-1323. doi: 復(fù)制

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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.
  1. 1. Jones LC, Hungerford DS. The pathogenesis of osteonecrosis. Instr Course Lect, 2007, 56: 179-196.
  2. 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. 3. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284(5411): 143-147.
  4. 4. Zipori D. The stem state: mesenchymal plasticity as a paradigm. Curr Stem Cell Res Ther, 2006, 1(1): 95-102.
  5. 5. McCarty DJ, Koopmann WJ. Arthritis and allied conditions: a textbook of rheumatology. 12th eds. Philadelphia: Lea & Febiger, 1993: 1677-1695.
  6. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 17. Oh SR, Sul OJ, Kim YY, et al. Saturated fatty acids enhance osteoclast survival. J Lipid Res, 2010, 51(5): 892-899.
  18. 18. Reid IR. Fat and bone. Arch Biochem Biophys, 2010, 503(1): 20-27.
  19. 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. 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. 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. 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.