NELL-1 in the treatment of osteoporotic bone loss

James, Aaron W.; Shen, Jia; Zhang, Xinli; Asatrian, Greg; Goyal, Raghav; Kwak, Jin Hee; Jiang, Lin; Bengs, Benjamin C.; Culiat, Cymbeline T.; Turner, A. Simon; Seim, Howard B.; Wu, Benjamin M.; Lyons, Karen M.; Adams, John S.; Ting, Kang; Soo, Chia

doi:10.1038/ncomms8362

Cited by 101 publications

(138 citation statements)

References 64 publications

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“…39 Tetrahedral 3D mesh models were generated using a random volume of interest within the defect site (size, 0.5 mm 3 ) using ScanIP software version 7 (Simpleware Ltd., Exeter, UK). Finite element analyses were performed using the ABAQUS software version 6.12 (Dassault Systèmes, Forest Hill, MD) with boundary conditions set as encastre, constrained in all directions.…”

Section: Biochemical Analysismentioning

confidence: 99%

“…Because NELL-1 was previously found to activate canonical Wnt signaling in both MSC and osteoclastic cell types, 39 we hypothesized that NELL-1emediated effects may involve canonical Wnt activation. We first examined in vitro activation of canonical Wnt signaling by immunocytochemical staining of M2-10B4 cells using an antibody against active b-catenin ( Figure 6A).…”

Section: Nell-1 Induces Canonical Wnt Signalingmentioning

confidence: 99%

“…Prior studies from our research group have confirmed that multiple cell types are NELL-1 responsive. For example, NELL-1 induction of osteogenesis is best studied in BMSCs 39 but also has been reported in committed osteoblasts, 67 adipose-derived stem cells, 72 and perivascular stem cells. 73,74 Although complex, Understanding the cellspecific responses to NELL-1 and BMP2 treatment may allow for future refinements in protein-based methods of tissue engineering.…”

Section: Cellular Effects Of Nell-1 and Bmp2 In Femoral Segmental Defmentioning

confidence: 99%

“…24,89 In support of this concept, mice homozygous for Nell1 deficiency exhibit reduced expression of the osteoclastogenesis inhibitor osteoprotegerin, 6 and the heterozygous Nell1-deficient mice that survive to adulthood manifest an osteoporotic phenotype. 39 Interestingly, BMP2 and Wnt signaling synergistically increase osteoprotegerin expression, 90 and ongoing studies will determine whether BMP2þNELL-1 can similarly induce osteoprotegerin and/or inhibit osteoclastogenesis.…”

Section: Nell-1 Enhances Bmp2 Osteogenesismentioning

confidence: 99%

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Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2

Shen

James

Zhang

et al. 2016

The American Journal of Pathology

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The differentiation factor NEL-like molecule-1 (NELL-1) has been reported as osteoinductive in multiple in vivo preclinical models. Bone morphogenetic protein (BMP)-2 is used clinically for skeletal repair, but in vivo administration can induce abnormal, adipose-filled, poorquality bone. We demonstrate that NELL-1 combined with BMP2 significantly optimizes osteogenesis in a rodent femoral segmental defect model by minimizing the formation of BMP2-induced adipose-filled cystlike bone. In vitro studies using the mouse bone marrow stromal cell line M2-10B4 and human primary bone marrow stromal cells have confirmed that NELL-1 enhances BMP2-induced osteogenesis and inhibits BMP2-induced adipogenesis. Importantly, the ability of NELL-1 to direct BMP2-treated cells toward osteogenesis and away from adipogenesis requires intact canonical Wnt signaling. Overall, these studies establish the feasibility of combining NELL-1 with BMP2 to improve clinical bone regeneration and provide mechanistic insight into canonical Wnt pathway activity during NELL-1 and BMP2 osteogenesis. The novel abilities of NELL-1 to stimulate Wnt signaling and to repress adipogenesis may highlight new treatment approaches for bone loss in osteoporosis. NEL-like molecule-1 (NELL-1) is an osteoinductive growth factor first identified through its overexpression in pathologically fusing suture specimens from patients with craniosynostosis. 1,2 Transgenic Nell1-overexpressing mice recapitulate craniosynostosis-like phenotypes, exhibiting gross calvarial bone overgrowth and increased osteoblast differentiation. 3 Conversely, Nell1 deficiency severely disrupts bone growth, as mice with nonsense mutations in Nell1 die perinatally with major skeletal anomalies in the craniofacial complex, spine, and long bones. 4e6 Highlighting the central role of NELL-1 in skeletal development, NELL-1 mediates key downstream effects of the master osteogenic regulator runt-related transcription factor 2 (RUNX2) 7 and can partially rescue RUNX2 loss of function. 8 NELL-1 can also transiently activate mitogen-activated protein kinase signaling to induce RUNX2 phosphorylation and osteogenic differentiation. 9 Recently, we

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Section: Biochemical Analysismentioning

confidence: 99%

Section: Nell-1 Induces Canonical Wnt Signalingmentioning

confidence: 99%

Section: Cellular Effects Of Nell-1 and Bmp2 In Femoral Segmental Defmentioning

confidence: 99%

Section: Nell-1 Enhances Bmp2 Osteogenesismentioning

confidence: 99%

See 2 more Smart Citations

Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2

Shen

James

Zhang

et al. 2016

The American Journal of Pathology

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“…Sections of neonatal rat spines were used in each instance as a positive staining control. 11 Sections were counterstained in Modified Mayers…”

Section: Histological and Immunohistochemical Analysesmentioning

confidence: 99%

NELL-1 expression in tumors of cartilage

Shen

LaChaud

Shrestha

et al. 2015

Journal of Orthopaedics

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Nanoflake Arrays of Lithiophilic Metal Oxides for the Ultra‐Stable Anodes of Lithium‐Metal Batteries

Tao

Mateti

et al. 2018

Adv Funct Materials

174

109

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A molten lithium infusion strategy has been proposed to prepare stable Li-metal anodes to overcome the serious issues associated with dendrite formation and infinite volume change during cycling of lithium-metal batteries. Stable host materials with superior wettability of molten Li are the prerequisite. Here, it is demonstrated that a series of strong oxidizing metal oxides, including MnO 2 , Co 3 O 4 , and SnO 2 , show superior lithiophilicity due to their high chemical reactivity with Li. Composite lithium-metal anodes fabricated via melt infusion of lithium into graphene foams decorated by these metal oxide nanoflake arrays successfully control the formation and growth of Li dendrites and alleviate volume change during cycling. A resulting Li-Mn/graphene composite anode demonstrates a super-long and stable lifetime for repeated Li plating/stripping of 800 cycles at 1 mA cm −2 without voltage fluctuation, which is eight times longer than the normal lifespan of a bare Li foil under the same conditions. Furthermore, excellent rate capability and cyclability are realized in full-cell batteries with Li-Mn/graphene composite anodes and LiCoO 2 cathodes. These results show a major advancement in developing a stable Li anode for lithium-metal batteries.

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NELL-1 in the treatment of osteoporotic bone loss

Cited by 101 publications

References 64 publications

Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2

Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2

NELL-1 expression in tumors of cartilage

Nanoflake Arrays of Lithiophilic Metal Oxides for the Ultra‐Stable Anodes of Lithium‐Metal Batteries

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