Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2
| Autor: | Janette N. Zara, Kevin S. Lee, Chia Soo, Kevork Khadarian, Sotirios Tetradis, Aaron W. James, Ronald K. Siu, Kang Ting, Jia Shen, Michael F. Chiang, Alan Nguyen, Shen Pang, Min Lee, Xinli Zhang, Greg Asatrian |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty animal structures Bone Regeneration Bone morphogenetic protein 8A Bone Morphogenetic Protein 2 Nerve Tissue Proteins Bone morphogenetic protein Bone morphogenetic protein 2 Pathology and Forensic Medicine 03 medical and health sciences Osteogenesis Internal medicine medicine Animals Humans Bone regeneration Adipogenesis Chemistry Calcium-Binding Proteins Wnt signaling pathway Mesenchymal Stem Cells Regular Article Cell biology Bone morphogenetic protein 7 030104 developmental biology Primary bone Endocrinology Rats Inbred Lew embryonic structures Signal Transduction |
| Zdroj: | The American journal of pathology. 186(2) |
| ISSN: | 1525-2191 |
| Popis: | 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, poor-quality 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. |
| Databáze: | OpenAIRE |
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