• 哈爾濱醫(yī)科大學(xué)附屬第一醫(yī)院骨科（哈爾濱，150001）;

目的 綜述Tenomodulin在肌腱組織工程中的研究現(xiàn)狀，展望其研究和應(yīng)用發(fā)展方向。 方法查閱近年關(guān)于Tenomodulin在肌腱組織工程中的相關(guān)研究文獻(xiàn)，并進(jìn)行分析總結(jié)。 結(jié)果Tenomodulin是一種Ⅱ型跨膜蛋白，具有調(diào)節(jié)肌腱組織發(fā)育作用，其C端具有抑制血管發(fā)生的活性作用。生物信息學(xué)特征分析Tenomodulin cDNA全長1 360 bp，定位于染色體Xq22.1上。多種細(xì)胞因子對(duì)Tenomodulin的表達(dá)具有調(diào)控作用，其中與堿性螺旋-環(huán)-螺旋轉(zhuǎn)錄因子Scleraxis關(guān)系最為密切；支架材料的性質(zhì)、結(jié)構(gòu)等對(duì)種子細(xì)胞Tenomodulin的表達(dá)也具有調(diào)控作用；應(yīng)力負(fù)載和傳代培養(yǎng)對(duì)Tenomodulin的表達(dá)具有一定影響。 結(jié)論Tenomodulin作為肌腱相對(duì)特異性標(biāo)記分子，開發(fā)和利用其C端血管發(fā)生抑制作用，將在肌腱組織工程中具有重要應(yīng)用潛力和前景。

引用本文： 關(guān)策文,雷星,宋揚(yáng),曲彥隆. Tenomodulin在肌腱組織工程中的研究現(xiàn)狀與展望. 中國修復(fù)重建外科雜志, 2013, 27(1): 101-105. doi: 復(fù)制

1. Rui YF, Lui PP, Li G, et al. Isolation and characterization of multipotent rat tendon-derived stem cells. Tissue Eng Part A, 2010, 16(5): 1549-1558.
2. Tan Q, Lui PP, Rui YF, et al. Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering. Tissue Eng Part A, 2012, 18(7-8): 840-851.
3. Alberton P, Popov C, Prägert M, et al. Conversion of human bone marrow-derived mesenchymal stem cells into tendon progenitor cells by ectopic expression of scleraxis. Stem Cells Dev, 2012, 21(6): 846-858.
4. Yukata K, Matsui Y, Shukunami C, et al. Differential expression of Tenomodulin and Chondromodulin-1 at the insertion site of the tendon reflects a phenotypic transition of the resident cells. Tissue Cell, 2010, 42(2): 116-120.
5. Backman LJ, Fong G, Andersson G, et al. Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation. PLoS One, 2011, 6(11): e27209.
6. Kishore V, Bullock W, Sun X, et al. Tenogenic differentiation of human MSCs induced by the topography of electrochemically aligned collagen threads. Biomaterials, 2012, 33(7): 2137-2144.
7. Shukunami C, Oshima Y, Hiraki Y. Molecular cloning of tenomodulin, a novel chondromodulin-I related gene. Biochem Biophys Res Commun, 2001, 280(5): 1323-1327.
8. Oshima Y, Sato K, Tashiro F, et al. Anti-angiogenic action of the C-terminal domain of tenomodulin that shares homology with chondromodulin-I. J Cell Sci, 2004, 117(Pt 13): 2731-2744.
9. Sánchez-Pulido L, Devos D, Valencia A. BRICHOS: a conserved domain in proteins associated with dementia, respiratory distress and cancer. Trends Biochem Sci, 2002, 27(7): 329-332.
10. Aslan H, Kimelman-Bleich N, Pelled G, et al. Molecular targets for tendon neoformation. J Clin Invest, 2008, 118(2): 439-444.
11. Shukunami C, Takimoto A, Miura S, et al. Chondromodulin-I and tenomodulin are differentially expressed in the avascular mesenchyme during mouse and chick development. Cell Tissue Res, 2008, 332(1): 111-122.
12. Shukunami C, Takimoto A, Oro M, et al. Scleraxis positively regulates the expression of tenomodulin, a differentiation marker of tenocytes. Dev Biol, 2006, 298(1): 234-247.
13. Docheva D, Hunziker EB, Fässler R, et al. Tenomodulin is necessary for tenocyte proliferation and tendon maturation. Mol Cell Biol, 2005, 25(2): 699-705.
14. Watahiki J, Yamaguchi T, Enomoto A, et al. Identification of differentially expressed genes in mandibular condylar and tibial growth cartilages using laser microdissection and fluorescent differential display: chondromodulin-I (ChM-1) and tenomodulin (TeM) are differentially expressed in mandibular condylar and other growth cartilages. Bone, 2008, 42(6): 1053-1060.
15. Pisani DF, Pierson PM, Massoudi A, et al. Myodulin is a novel potential angiogenic factor in skeletal muscle. Exp Cell Res, 2004, 292(1): 40-50.
16. Shukunami C, Hiraki Y. Chondromodulin-I and tenomodulin: the negative control of angiogenesis in connective tissue. Curr Pharm Des, 2007, 13(20): 2101-2112.
17. Kimura N, Shukunami C, Hakuno D, et al. Local tenomodulin absence, angiogenesis, and matrix metalloproteinase activation are associated with the rupture of the chordae tendineae cordis. Circulation, 2008, 118(17): 1737-1747.
18. Hiraki Y, Shukunami C. Angiogenesis inhibitors localized in hypovascular mesenchymal tissues: chondromodulin-I and tenomodulin. Connect Tissue Res, 2005, 46(1): 3-11.
19. Lorda-Diez CI, Montero JA, Martinez-Cue C, et al. Transforming growth factors beta coordinate cartilage and tendon differentiation in the developing limb mesenchyme. J Biol Chem, 2009, 284(43): 29988-29996.
20. Schneider PR, Buhrmann C, Mobasheri A, et al. Three-dimensional high-density co-culture with primary tenocytes induces tenogenic differentiation in mesenchymal stem cells. J Orthop Res, 2011, 29(9): 1351-1360.
21. Liu W, Watson SS, Lan Y, et al. The atypical homeodomain transcription factor Mohawk controls tendon morphogenesis. Mol Cell Biol, 2010, 30(20): 4797-4807.
22. Inoue M, Ebisawa K, Itaya T, et al. Effect of GDF-5 and BMP-2 on the expression of tendo/ligamentogenesis-related markers in human PDL-derived cells. Oral Dis, 2012, 18(2): 206-212.
23. Park A, Hogan MV, Kesturu GS, et al. Adipose-derived mesenchymal stem cells treated with growth differentiation factor-5 express tendon-specific markers. Tissue Eng Part A, 2010, 16(9): 2941-2951.
24. Haddad-Weber M, Prager P, Kunz M, et al. BMP12 and BMP13 gene transfer induce ligamentogenic differentiation in mesenchymal progenitor and anterior cruciate ligament cells. Cytotherapy, 2010, 12(4): 505-513.
25. Violini S, Ramelli P, Pisani LF, et al. Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12. BMC Cell Biol, 2009, 10: 29.
26. 倪明, 芮云峰, 陳啟明, 等. 生長分化因子7體外促進(jìn)BMSCs向肌腱細(xì)胞分化的研究. 中國修復(fù)重建外科雜志, 2011, 25(9): 1103-1109.
27. Lee JY, Zhou Z, Taub PJ, et al. BMP-12 treatment of adult mesenchymal stem cells in vitro augments tendon-like tissue formation and defect repair in vivo. PloS One, 2011, 6(3): e17531.
28. Mendias CL, Bakhurin KI, Faulkner JA. Tendons of myostatin-deficient mice are small, brittle, and hypocellular. Proc Natl Acad Sci U S A, 2008, 105(1): 388-393.
29. Engler AJ, Sen S, Sweeney HL, et al. Matrix elasticity directs stem cell lineage specification. Cell, 2006, 126(4): 677-689.
30. Kilian KA, Bugarija B, Lahn BT, et al. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci U S A, 2010, 107(11): 4872-4877.
31. Kishore V, Bullock W, Sun X, et al. Tenogenic differentiation of human MSCs induced by the topography of electrochemically aligned collagen threads. Biomaterials, 2012, 33(7): 2137-2144.
32. Omae H, Zhao C, Sun YL, et al. Multilayer tendon slices seeded with bone marrow stromal cells: a novel composite for tendon engineering. J Orthop Res, 2009, 27(7): 937-942.
33. Omae H, Sun YL, An KN, et al. Engineered tendon with decellularized xenotendon slices and bone marrow stromal cells: an in vivo animal study. J Tissue Eng Regen Med, 2012, 6(3): 238-244.
34. Bashur CA, Shaffer RD, Dahlgren LA, et al. Effect of fiber diameter and alignment of electrospun polyurethane meshes on mesenchymal progenitor cells. Tissue Eng Part A, 2009, 15(9): 2435-2445.
35. Zhu J, Li J, Wang B, et al. The regulation of phenotype of cultured tenocytes by microgrooved surface structure. Biomaterials, 2010, 31(27): 6952-6958.
36. Eliasson P, Andersson T, Aspenberg P. Rat Achilles tendon healing: mechanical loading and gene expression. J Appl Physiol, 2009, 107(2): 399-407.
37. Mendias CL, Gumucio JP, Bakhurin KI, et al. Physiological loading of tendons induces scleraxis expression in epitenon fibroblasts. J Orthop Res, 2012, 30(4): 606-612.
38. 廖梅旭, 寧良菊, 陳曉禾, 等. 應(yīng)變誘導(dǎo)BMSCs腱向分化的實(shí)驗(yàn)研究. 中國修復(fù)重建外科雜志, 2010, 24(7): 817-821.
39. Tan Q, Lui PP, Rui YF. Effect of in vitro passaging on the stem cell-related properties of tendon-derived stem cells-implications in tissue engineering. Stem Cells Dev, 2012, 21(5): 790-800.
40. Mazzocca AD, Chowaniec D, McCarthy MB, et al. In vitro changes in human tenocyte cultures obtained from proximal biceps tendon: multiple passages result in changes in routine cell markers. Knee Surg Sports Traumatol Arthrosc, 2012, 20(9): 1666-1672.
  1. 1. Rui YF, Lui PP, Li G, et al. Isolation and characterization of multipotent rat tendon-derived stem cells. Tissue Eng Part A, 2010, 16(5): 1549-1558.
  2. 2. Tan Q, Lui PP, Rui YF, et al. Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering. Tissue Eng Part A, 2012, 18(7-8): 840-851.
  3. 3. Alberton P, Popov C, Prägert M, et al. Conversion of human bone marrow-derived mesenchymal stem cells into tendon progenitor cells by ectopic expression of scleraxis. Stem Cells Dev, 2012, 21(6): 846-858.
  4. 4. Yukata K, Matsui Y, Shukunami C, et al. Differential expression of Tenomodulin and Chondromodulin-1 at the insertion site of the tendon reflects a phenotypic transition of the resident cells. Tissue Cell, 2010, 42(2): 116-120.
  5. 5. Backman LJ, Fong G, Andersson G, et al. Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation. PLoS One, 2011, 6(11): e27209.
  6. 6. Kishore V, Bullock W, Sun X, et al. Tenogenic differentiation of human MSCs induced by the topography of electrochemically aligned collagen threads. Biomaterials, 2012, 33(7): 2137-2144.
  7. 7. Shukunami C, Oshima Y, Hiraki Y. Molecular cloning of tenomodulin, a novel chondromodulin-I related gene. Biochem Biophys Res Commun, 2001, 280(5): 1323-1327.
  8. 8. Oshima Y, Sato K, Tashiro F, et al. Anti-angiogenic action of the C-terminal domain of tenomodulin that shares homology with chondromodulin-I. J Cell Sci, 2004, 117(Pt 13): 2731-2744.
  9. 9. Sánchez-Pulido L, Devos D, Valencia A. BRICHOS: a conserved domain in proteins associated with dementia, respiratory distress and cancer. Trends Biochem Sci, 2002, 27(7): 329-332.
  10. 10. Aslan H, Kimelman-Bleich N, Pelled G, et al. Molecular targets for tendon neoformation. J Clin Invest, 2008, 118(2): 439-444.
  11. 11. Shukunami C, Takimoto A, Miura S, et al. Chondromodulin-I and tenomodulin are differentially expressed in the avascular mesenchyme during mouse and chick development. Cell Tissue Res, 2008, 332(1): 111-122.
  12. 12. Shukunami C, Takimoto A, Oro M, et al. Scleraxis positively regulates the expression of tenomodulin, a differentiation marker of tenocytes. Dev Biol, 2006, 298(1): 234-247.
  13. 13. Docheva D, Hunziker EB, Fässler R, et al. Tenomodulin is necessary for tenocyte proliferation and tendon maturation. Mol Cell Biol, 2005, 25(2): 699-705.
  14. 14. Watahiki J, Yamaguchi T, Enomoto A, et al. Identification of differentially expressed genes in mandibular condylar and tibial growth cartilages using laser microdissection and fluorescent differential display: chondromodulin-I (ChM-1) and tenomodulin (TeM) are differentially expressed in mandibular condylar and other growth cartilages. Bone, 2008, 42(6): 1053-1060.
  15. 15. Pisani DF, Pierson PM, Massoudi A, et al. Myodulin is a novel potential angiogenic factor in skeletal muscle. Exp Cell Res, 2004, 292(1): 40-50.
  16. 16. Shukunami C, Hiraki Y. Chondromodulin-I and tenomodulin: the negative control of angiogenesis in connective tissue. Curr Pharm Des, 2007, 13(20): 2101-2112.
  17. 17. Kimura N, Shukunami C, Hakuno D, et al. Local tenomodulin absence, angiogenesis, and matrix metalloproteinase activation are associated with the rupture of the chordae tendineae cordis. Circulation, 2008, 118(17): 1737-1747.
  18. 18. Hiraki Y, Shukunami C. Angiogenesis inhibitors localized in hypovascular mesenchymal tissues: chondromodulin-I and tenomodulin. Connect Tissue Res, 2005, 46(1): 3-11.
  19. 19. Lorda-Diez CI, Montero JA, Martinez-Cue C, et al. Transforming growth factors beta coordinate cartilage and tendon differentiation in the developing limb mesenchyme. J Biol Chem, 2009, 284(43): 29988-29996.
  20. 20. Schneider PR, Buhrmann C, Mobasheri A, et al. Three-dimensional high-density co-culture with primary tenocytes induces tenogenic differentiation in mesenchymal stem cells. J Orthop Res, 2011, 29(9): 1351-1360.
  21. 21. Liu W, Watson SS, Lan Y, et al. The atypical homeodomain transcription factor Mohawk controls tendon morphogenesis. Mol Cell Biol, 2010, 30(20): 4797-4807.
  22. 22. Inoue M, Ebisawa K, Itaya T, et al. Effect of GDF-5 and BMP-2 on the expression of tendo/ligamentogenesis-related markers in human PDL-derived cells. Oral Dis, 2012, 18(2): 206-212.
  23. 23. Park A, Hogan MV, Kesturu GS, et al. Adipose-derived mesenchymal stem cells treated with growth differentiation factor-5 express tendon-specific markers. Tissue Eng Part A, 2010, 16(9): 2941-2951.
  24. 24. Haddad-Weber M, Prager P, Kunz M, et al. BMP12 and BMP13 gene transfer induce ligamentogenic differentiation in mesenchymal progenitor and anterior cruciate ligament cells. Cytotherapy, 2010, 12(4): 505-513.
  25. 25. Violini S, Ramelli P, Pisani LF, et al. Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12. BMC Cell Biol, 2009, 10: 29.
  26. 26. 倪明, 芮云峰, 陳啟明, 等. 生長分化因子7體外促進(jìn)BMSCs向肌腱細(xì)胞分化的研究. 中國修復(fù)重建外科雜志, 2011, 25(9): 1103-1109.
  27. 27. Lee JY, Zhou Z, Taub PJ, et al. BMP-12 treatment of adult mesenchymal stem cells in vitro augments tendon-like tissue formation and defect repair in vivo. PloS One, 2011, 6(3): e17531.
  28. 28. Mendias CL, Bakhurin KI, Faulkner JA. Tendons of myostatin-deficient mice are small, brittle, and hypocellular. Proc Natl Acad Sci U S A, 2008, 105(1): 388-393.
  29. 29. Engler AJ, Sen S, Sweeney HL, et al. Matrix elasticity directs stem cell lineage specification. Cell, 2006, 126(4): 677-689.
  30. 30. Kilian KA, Bugarija B, Lahn BT, et al. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci U S A, 2010, 107(11): 4872-4877.
  31. 31. Kishore V, Bullock W, Sun X, et al. Tenogenic differentiation of human MSCs induced by the topography of electrochemically aligned collagen threads. Biomaterials, 2012, 33(7): 2137-2144.
  32. 32. Omae H, Zhao C, Sun YL, et al. Multilayer tendon slices seeded with bone marrow stromal cells: a novel composite for tendon engineering. J Orthop Res, 2009, 27(7): 937-942.
  33. 33. Omae H, Sun YL, An KN, et al. Engineered tendon with decellularized xenotendon slices and bone marrow stromal cells: an in vivo animal study. J Tissue Eng Regen Med, 2012, 6(3): 238-244.
  34. 34. Bashur CA, Shaffer RD, Dahlgren LA, et al. Effect of fiber diameter and alignment of electrospun polyurethane meshes on mesenchymal progenitor cells. Tissue Eng Part A, 2009, 15(9): 2435-2445.
  35. 35. Zhu J, Li J, Wang B, et al. The regulation of phenotype of cultured tenocytes by microgrooved surface structure. Biomaterials, 2010, 31(27): 6952-6958.
  36. 36. Eliasson P, Andersson T, Aspenberg P. Rat Achilles tendon healing: mechanical loading and gene expression. J Appl Physiol, 2009, 107(2): 399-407.
  37. 37. Mendias CL, Gumucio JP, Bakhurin KI, et al. Physiological loading of tendons induces scleraxis expression in epitenon fibroblasts. J Orthop Res, 2012, 30(4): 606-612.
  38. 38. 廖梅旭, 寧良菊, 陳曉禾, 等. 應(yīng)變誘導(dǎo)BMSCs腱向分化的實(shí)驗(yàn)研究. 中國修復(fù)重建外科雜志, 2010, 24(7): 817-821.
  39. 39. Tan Q, Lui PP, Rui YF. Effect of in vitro passaging on the stem cell-related properties of tendon-derived stem cells-implications in tissue engineering. Stem Cells Dev, 2012, 21(5): 790-800.
  40. 40. Mazzocca AD, Chowaniec D, McCarthy MB, et al. In vitro changes in human tenocyte cultures obtained from proximal biceps tendon: multiple passages result in changes in routine cell markers. Knee Surg Sports Traumatol Arthrosc, 2012, 20(9): 1666-1672.