NELL-1促成骨和成软骨的作用机制及应用前景

Abstract

Abstract: NELL-1 (neural epidermal growth factor-like 1), as a growth factor with high specificity to osteochondrocyte cell line, has been paid close attention to because of its effect of inducing bone formation locally. In addition, it also has the osteogenic potential as a systemic therapeutic drug and the function of promoting cartilage formation. In terms of osteogenesis, NELL-1 mainly takes effect through Runx2, MAPK signaling pathway, and classical Wnt signaling pathway, and it has a synergistic effect with the classical osteogenic factor BMPs. In recent years, due to the continuous progress of bioinformatics and high-throughput RNA sequencing, researchers have also discovered the potential regulatory role of RNA network when NELL-1 promotes osteogenesis. The chondrogenic activity of NELL-1 mainly depends on the Ihh signal transduction mediated by Runx3. This article mainly reviews the related mechanisms of NELL-1 in promoting osteogenesis and chondrogenesis, and its application in the field of bone tissue regeneration and cartilage tissue regeneration.

Key words: NELL-1, osteogenesis, chondrogenesis, Osteoporosis, Osteoarthritis

CLC Number:

R780.2

Shi-Yu HU. The action mechanism and application prospects of NELL-1 in promoting osteogenesis and chondrogenesis[J]. , 2021, 41(6): 545-550.

References 64

[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-

The action mechanism and application prospects of NELL-1 in promoting osteogenesis and chondrogenesis

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References 64

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	. High concentration of zoledronate inhibits osteogenesis differentiation and promotes apoptosis of human periodontal ligament stem cell [J]. , 2019, 39(10): 880-888.
[2]	. Analysis of GNAS mutations and biological characteristics of bone marrow stromal cells in fibrous dysplasia of the jaws [J]. , 2018, 38(4): 289-294.
[3]	. The role of lateral pterygoid muscle in traumatic temporomandibular joint ankylosis [J]. , 2018, 38(3): 211-216.
[4]	. Research progress of effects of macrophages on the osteogenic differentiation of mesenchymal stem cells and the underneath mechanisms [J]. , 2018, 38(11): 1026-1030.
[5]	Rui ZHANG. Research progress of the potential use of metformin [J]. , 2018, 38(10): 938-941.
[6]	. Effect of altered mastication on the osteogenesis of condylar cartilage [J]. , 2018, 38(10): 868-871.
[7]	. Analysis of periodontal status in patients with chronic periodontitis in the post - menopausal period in Northeast China [J]. , 2018, 38(1): 44-47.
[8]	. Research progress of effects of TGF-βon the development, growth remodeling and degradation of mandibular condylar cartilage [J]. , 2018, 38(1): 78-82.
[9]	. Research progress of dental stem cells in alveolar bone regeneration [J]. , 2017, 37(8): 755-759.
[10]	. The study of microRNA-145（miR-145）modulating osteogenesis differentiation of rat bone marrow mesenchymal stem cells（rBMMSC） [J]. , 2017, 37(8): 693-697.
[11]	. The research development of miRNAs in bone metabolism. [J]. , 2017, 37(3): 276-280.
[12]	. Research progress of the accelerated distal movement of canine by periodontal ligament distraction osteogenesis [J]. , 2017, 37(12): 1135-1138.
[13]	He Sheng. Effects of osteoporosis on stability of osseointegrated implants [J]. , 2017, 37(11): 991-996.
[14]	. Experimental study of inducing an osteoarthritis-like lesion in the rat temporamandibular joint by mouth-opening [J]. , 2016, 36(5): 390-393.
[15]	. The research progress between PTH1-34 and impants osseointegration [J]. , 2016, 36(2): 189-192.