›› 2021, Vol. 41 ›› Issue (6): 545-550.
胡诗余,施洁珺,胡济安
收稿日期:
2020-08-12
修回日期:
2020-09-17
出版日期:
2021-06-28
发布日期:
2021-06-25
通讯作者:
胡济安
E-mail:Hja@zju.edu.cn
基金资助:
Shi-Yu HU1,
Received:
2020-08-12
Revised:
2020-09-17
Online:
2021-06-28
Published:
2021-06-25
摘要: NELL-1(neural epidermal growth factor-like 1)是一种对骨软骨细胞系具有高度特异性的生长因子,因其局部诱导骨形成的效应而受到密切关注;另外,它还具有作为全身治疗药物的成骨潜能以及促软骨形成的功能。促成骨方面,NELL-1主要通过Runx、MAPK信号通路、经典Wnt信号通路起作用,和经典的成骨因子BMPs存在协同作用。最近几年,由于生物信息学和高通量RNA测序的不断进步,研究者也发现了NELL-1促成骨分化时RNA网络的潜在调控作用。而NELL-1的促软骨形成活性主要依赖于Runx3介导的Ihh信号转导。本文主要就NELL-1促进成骨和成软骨的相关机制,以及其在骨组织再生、软骨组织再生领域的应用作一综述。
中图分类号:
胡诗余 施洁珺 胡济安. NELL-1促成骨和成软骨的作用机制及应用前景[J]. 口腔医学, 2021, 41(6): 545-550.
Shi-Yu HU. The action mechanism and application prospects of NELL-1 in promoting osteogenesis and chondrogenesis[J]. Stomatology, 2021, 41(6): 545-550.
[1] | Yeh TT, Wu SS, Lee CH, et al.The short-term therapeutic effect of recombinant human bone morphogenetic protein-2 on collagenase-induced lumbar facet joint osteoarthritis in rats[J].Osteoarthritis Cartilage, 2007, 15(12):1357-1366 |
[2] | Watanabe TK, Katagiri T, Suzuki M, et al.Cloning and characterization of two novel human cDNAs (NELL1 and NELL2) encoding proteins with six EGF-like repeats[J].Genomics, 1996, 38(3):273-276 |
[3] | Ting K, Vastardis H, Mulliken JB, et al.Human NELL-1 expressed in unilateral coronal synostosis[J].J Bone Miner Res, 1999, 14(1):80-89 |
[4] | Zhang X, Zara J, Siu RK, et al.The role of NELL-1,a growth factor associated with craniosynostosis,in promoting bone regeneration[J].J Dent Res, 2010, 89(9):865-878 |
[5] | Kuroda S, Oyasu M, Kawakami M, et al.Biochemical characterization and expression analysis of neural thrombospondin-1-like proteins NELL1 and NELL2[J].Biochem Biophys Res Commun, 1999, 265(1):79-86 |
[6] | Li C, Zheng Z, Ha P, et al.Neurexin superfamily cell membrane receptor Contactin-Associated Protein Like-4 (Cntnap4) is involved in Neural EGFL-Like 1 (Nell-1)-responsive osteogenesis[J].J Bone Miner Res, 2018, 33(10):1813-1825 |
[7] | Mathieu F, Etain B, Dizier MH, et al.Genetics of emotional reactivity in bipolar disorders[J].J Affect Disord, 2015, 188:101-106 |
[8] | Zhang X, Cowan CM, Jiang X, et al.Nell-1 induces acrania-like cranioskeletal deformities during mouse embryonic development[J].Lab Invest, 2006, 86(7):633-644 |
[9] | Shen J, LaChaud G, Khadarian K, et al.NELL-1 expression in benign and malignant bone tumors[J].Biochem Biophys Res Commun, 2015, 460(2):368-374 |
[10] | Shen J, LaChaud G, Shrestha S, et al.NELL-1 expression in tumors of cartilage[J].J Orthop, 2015, 12(Suppl 2):S223-S229 |
[11] | Zhang X, Kuroda S, Carpenter D, et al.Craniosynostosis in transgenic mice overexpressing Nell-1[J].J Clin Invest, 2002, 110(6):861-870 |
[12] | Shen M, Wang G, Wang Y, et al.Nell-1 enhances osteogenic differentiation of pre-osteoblasts on titanium surfaces via the MAPK-ERK signaling pathway[J].Cell Physiol Biochem, 2018, 50(4):1522-1534 |
[13] | Cowan CM, Jiang X, Hsu T, et al.Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts[J].J Bone Miner Res, 2007, 22(6):918-930 |
[14] | James AW, Pang S, Askarinam A, et al.Additive effects of sonic Hedgehog and Nell-1 signaling in osteogenic versus adipogenic differentiation of human adipose-derived stromal cells[J].Stem Cells Dev, 2012, 21(12):2170-2178 |
[15] | Chung CG, James AW, Asatrian G, et al.Human perivascular stem cell-based bone graft substitute induces rat spinal fusion[J].Stem Cell Transl Med, 2014, 3(10):1231-1241 |
[16] | Lee S, Zhang X, Shen J, et al.hPSCs and NELL-1 synergistically enhance spinal fusion in osteoporotic rats[J].Stem Cells, 2015, 33(10):3158-3163 |
[17] | Pang S, Shen J, Liu Y, et al.Proliferation and osteogenic differentiation of mesenchymal stem cells induced by a short isoform of NELL-1[J].Stem Cells, 2015, 33(3):904-915 |
[18] | Meyers CA, Sun Z, Chang L, et al.Age dependent effects of NELL-1 isoforms on bone marrow stromal cells[J].J Orthopaedics, 2019, 16(2):175-178 |
[19] | Li W, Lee M, Whang J, et al.Delivery of lyophilized Nell-1 in a rat spinal fusion model[J].Tissue Eng Part A, 2010, 16(9):2861-2870 |
[20] | Siu RK, Lu SS, Li W, et al.Nell-1 protein promotes bone formation in a sheep spinal fusion model[J].Tissue Eng Part A, 2011, 17(7-8):1123-1135 |
[21] | Lee S, Wang C, Pan HS, et al.Combining Smoothened Agonist (SAG) and NEL-like protein-1 (NELL-1) enhances bone healing[J].Plast Reconstr Surg, 2017, 139(6):1385-1396 |
[22] | James AW, Chiang M, Asatrian G, et al.Vertebral implantation of NELL-1 enhances bone formation in an osteoporotic sheep model[J].Tissue Eng Part A, 2016, 22(11-12):840-849 |
[23] | James AW, Shen J, Tsuei R, et al.NELL-1 induces Sca-1+ mesenchymal progenitor cell expansion in models of bone maintenance and repair[J].JCI Insight, 2017, 2(12):e92573- |
[24] | Kwak J, Zara JN, Chiang M, et al.NELL-1 injection maintains long-bone quantity and quality in an ovariectomy-induced osteoporotic senile rat model[J].Tissue Eng Part A, 2013, 19(34):426-436 |
[25] | James AW, Shen J, Zhang X, et al.NELL-1 in the treatment of osteoporotic bone loss[J].Nat Commun, 2015, 6:7362- |
[26] | Li W, Zara JN, Siu RK, et al.Nell-1 enhances bone regeneration in a rat critical-sized femoral segmental defect model[J].Plast Reconstr Surg, 2011, 127(2):580-577 |
[27] | Desai J, Shannon ME, Johnson MD, et al.Nell1-deficient mice have reduced expression of extracellular matrix proteins causing cranial and vertebral defects[J].Hum Mol Genet, 2006, 15(8):1329-1341 |
[28] | Qi H, Kim JK, Ha P, et al.Inactivation of Nell-1 in chondrocytes significantly impedes appendicular skeletogenesis[J].J Bone Miner Res, 2019, 34(3):533-546 |
[29] | Chen X, Wang H, Yu M, et al.Cumulative inactivation of Nell-1 in Wnt1 expressing cell lineages results in craniofacial skeletal hypoplasia and postnatal hydrocephalus[J].Cell Death Differ, 2020, 27(4):1415-1430 |
[30] | Komori T.Regulation of osteoblast differentiation by transcription factors[J].J Cell Biochem, 2006, 99(5):1233-1239 |
[31] | Banerjee C, McCabe LR, Choi JY, et al.Runt homology domain proteins in osteoblast differentiation: AML3CBFA1 is a major component of a bone-specific complex[J].J Cell Biochem, 1997, 66(1):1-8 |
[32] | Komori T, Yagi H, Nomura S, et al.Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts[J].Cell, 1997, 89(5):755-764 |
[33] | Truong T, Zhang X, Pathmanathan D, et al.Craniosynostosis-associated gene Nell-1 is regulated by Runx2[J].J Bone Miner Res, 2007, 22(1):7-18 |
[34] | Chen F, Zhang X, Sun S, et al.NELL-1,an osteoinductive factor,is a direct transcriptional target of Osterix[J].PLoS ONE, 2011, 6(9):e24638- |
[35] | Bokui N, Otani T, Igarashi K, et al.Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation[J].FEBS Lett, 2008, 582(2):365-371 |
[36] | Lee KS, Hong SH, Bae SC.Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following induction by transforming growth factor-beta and bone morphogenetic protein[J].Oncogene, 2002, 21(47):7156-7163 |
[37] | Chen F, Walder B, James AW, et al.NELL-1-dependent mineralisation of Saos-2 human osteosarcoma cells is mediated via c-Jun N-terminal kinase pathway activation[J].Int Orthop, 2012, 36(10):2181-2187 |
[38] | Cai T, Sun D, Duan Y, et al.Wntb-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression[J].Exp Cell Res, 2016, 345(2):206-217 |
[39] | Shen J, James AW, Zhang X, et al.Novel Wnt regulator NEL-like molecule-1 antagonizes adipogenesis and augments osteogenesis induced by bone morphogenetic protein 2[J].Am J Pathol, 2016, 186(2):419-434 |
[40] | Rice D, Kim H, Thesleff I, et al.Apoptosis in murine calvarial bone and suture development[J].Eur J Oral Sci, 1999, 107(4):265-275 |
[41] | Zhang X, Carpenter D, Bokui N, et al.Overexpression of Nell-1,a craniosynostosis-associated gene,induces apoptosis in osteoblasts during craniofacial development[J].J Bone Miner Res, 2003, 18(12):2126-2134 |
[42] | Pakvasa M, Alverdy A, Mostafa S, et al.Neural EGF-like protein 1 (NELL-1): signaling crosstalk in mesenchymal stem cells and applications in regenerative medicine[J].Genes Dis, 2017, 4(3):127-137 |
[43] | Shen J, James AW, Zara JN, et al.BMP2-Induced Inflammation Can Be Suppressed by the Osteoinductive Growth Factor Nell-1[J].Tissue Eng Part A, 2013, 19(21-22):2390-2401 |
[44] | Liu L, Lam WMR, Naidu M, et al.Synergistic Effect of NELL-1 and an Ultra-Low Dose of BMP-2 on Spinal Fusion[J].Tissue Eng Part A, 2019, 25(23-24):1677-1689 |
[45] | Fahmy-Garcia S, van Driel M, Witte-Buoma J, et al.NELL-1,HMGB1,and CCN2 enhance migration and vasculogenesis,but not osteogenic differentiation compared to BMP2[J].Tissue Eng Part A, 2018, 24(3):207-218 |
[46] | Wang J, Liao J, Zhang F, et al.NEL-Like Molecule-1 (Nell1) is regulated by Bone Morphogenetic Protein 9 (BMP9) and potentiates BMP9-induced osteogenic differentiation at the expense of adipogenesis in mesenchymal stem cells[J].Cell Physiol Biochem, 2017, 41(2):484-500 |
[47] | Salmena L, Poliseno L, Tay Y, et al.A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?[J].Cell, 2011, 146(3):353-358 |
[48] | Huang X, Cen X, Zhang B, et al.The roles of circRFWD2 and circINO80 during NELL‐1‐induced osteogenesis[J].J Cell Mol Med, 2019, 23(12):8432-8441 |
[49] | Yu L, Cen X, Xia K, et al.microRNA expression profiles and the potential competing endogenous RNA networks in NELL‐1‐induced human adipose‐derived stem cell osteogenic differentiation[J].J Cell Biochem, 2020, :1-19 |
[50] | Zhang Y, Dong R, Park Y, et al.Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles[J].Int J Pharmaceut, 2016, 511(1):79-89 |
[51] | Li Y, Song H, Xiong S, et al.Chitosan-stablized bovine serum albumin nanoparticles having ability to control the release of NELL-1 protein[J].Int J Biol Macromol, 2018, 109:672-680 |
[52] | Zhang J, Chen Y, Xu J, et al.Tissue engineering using 3D printed nano-bioactive glass loaded with NELL1 gene for repairing alveolar bone defects[J].Regen Biomater, 2018, 5(4):213-220 |
[53] | Zhang Y, Velasco O, Zhang X, et al.Bioactivity and circulation time of PEGylated NELL-1 in mice and the potential for osteoporosis therapy[J].Biomaterials, 2014, 35(24):6614-6621 |
[54] | Kwak JH, Zhang Y, Park J, et al.Pharmacokinetics and osteogenic potential of PEGylated NELL-1 in vivo after systemic administration[J].Biomaterials, 2015, 57:73-83 |
[55] | Tanjaya J, Zhang Y, Lee S, et al.Efficacy of intraperitoneal administration of PEGylated NELL-1 for bone formation[J].BioResearch Open Access, 2016, 5(1):159-170 |
[56] | Tanjaya J, Lord EL, Wang C, et al.The Effects of Systemic Therapy of PEGylated Nell-1 on Fracture Healing in Mice[J].Am J Pathol, 2018, 188(3):715-727 |
[57] | Li CS, Zhang X, Péault B, et al.Accelerated Chondrogenic Differentiation of Human Perivascular Stem Cells with NELL-1[J].Tissue Eng Part A, 2016, 22(3-4):272-285 |
[58] | Lee M, Siu RK, Ting K, et al.Effect of Nell-1 delivery on chondrocyte proliferation and cartilaginous extracellular matrix deposition[J].Tissue Eng Part A, 2010, 16(5):1791-1800 |
[59] | Siu RK, Zara JN, Hou Y, et al.NELL-1 promotes cartilage regeneration in an in vivo rabbit model[J].Tissue Eng Part A, 2012, 18(3-4):252-261 |
[60] | Li C, Jiang J, Zheng Z, et al.Neural EGFL-Like 1 is a downstream regulator of Runt-related transcription factor 2 in chondrogenic differentiation and maturation[J].Am J Pathol, 2017, 187(5):963-972 |
[61] | Li C, Zheng Z, Jiang J, et al.Neural EGFL-like 1 regulates cartilage maturation through Runt-related transcription factor 3-mediated Indian hedgehog signaling[J].Am J Pathol, 2018, 188(2):392-403 |
[62] | Li C, Zheng Z, Zhang X, et al.Nfatc1 is a functional transcriptional factor mediating Nell-1-induced Runx3 upregulation in chondrocytes[J].Int J Mol Sci, 2018, 19(1):e168- |
[63] | 李雪燕, 肖迪, 陈瞰, 等.骨关节炎下颞下颌关节注射Nell-1对关节软骨保护作用的研究[J].现代口腔医学杂志, 2017, (1):1-5 |
[64] | Li C, Zheng Z, Ha P, et al.Neural EGFL like 1 as a potential pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug[J].Biomaterials, 2020, 226:119541- |
[1] | 朱珠 张玮. 川续断皂苷Ⅵ对小鼠成肌细胞成骨分化的影响[J]. , 2021, 41(5): 398-402. |
[2] | 李若涵 佘文婷 华超 骆瑜 彭友俭. 肝细胞生长因子对成骨细胞增殖、凋亡及成骨分化的影响[J]. , 2020, 40(8): 688-691. |
[3] | 王莉莉 严佳 李东升 莫秀梅 胡小坤 章非敏 刘梅. 两种新型胶原膜引导骨组织再生的体内外性能研究[J]. , 2019, 39(6): 481-487. |
[4] | 钱海馨 张富强. 微弧氧化钛表面对2型糖尿病大鼠骨髓基质干细胞成骨分化与种植体骨结合的影响[J]. , 2019, 39(12): 1062-1067. |
[5] | 李萌宇 俞叶佳 施越琦 戈旌 王绍义. 高浓度唑来膦酸对人牙周膜干细胞凋亡及成骨分化影响的实验研究[J]. , 2019, 39(10): 880-888. |
[6] | 王海锋 刘亚男 刘思思 宁美芝 幸丹 李文峰 曹钰. CD24基因调控根尖牙乳头干细胞的成骨分化功能[J]. , 2018, 38(7): 582-586. |
[7] | 胡姝颖 陈汉帮 陈刚 周雪锋 刘俊 章非敏. “壳-芯”结构电纺纤维膜对MC3T3-E1细胞体外早期成骨分化的影响[J]. , 2018, 38(6): 485-490. |
[8] | 肖涛 傅瑜 朱伟文 徐玲 张平 江宏兵. 颌骨骨纤维异常增殖症GNAS基因突变分析及其间充质细胞体外生物学特征[J]. , 2018, 38(4): 289-294. |
[9] | 左婕 王智亨 盛丽 袁晓娟 颜露 刘奕杉. miR-335对牙囊干细胞成骨分化能力的影响[J]. , 2018, 38(12): 1074-1078. |
[10] | 杨爽. 牙囊细胞成骨分化的研究进展[J]. , 2018, 38(10): 930-933. |
[11] | 何东萍 罗应伟. TGF-β在下颌髁突软骨的发育和改建中作用研究进展[J]. , 2018, 38(1): 78-82. |
[12] | 沈树平 陆亚倩 郑旸 张玮 朱庆萍. microRNA-145调控大鼠骨髓间充质干细胞成骨分化的实验研究[J]. , 2017, 37(8): 693-697. |
[13] | 李多多 王志峰 蓝菁. microRNAs在骨代谢中的研究进展[J]. , 2017, 37(3): 276-280. |
[14] | 李珊珊 张瑾. 微小RNA与肿瘤坏死因子-α对成骨分化调控作用研究进展[J]. , 2017, 37(2): 180-183. |
[15] | 陈红 刘东旭 杜丽玲 张译文. 力学刺激下BMP信号通路影响成骨分化的研究进展[J]. , 2017, 37(2): 162-165. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||