title: BMP7-Based Functionalized Self-Assembling Peptides Protect Nucleus Pulposus-Derived Stem Cells From Apoptosis In Vitro.
abstract: Tissue engineering has shown great success in the treatment of intervertebral disk degeneration (IVDD) in the past decade. However, the adverse and harsh microenvironment associated in the intervertebral disks remains a great obstacle for the survival of transplanted cells. Although increasing numbers of new materials have been created or modified to overcome this hurdle, a new effective strategy of biological therapy is still required. In this study, bone morphogenic protein 7 (BMP7)-based functionalized self-assembling peptides were developed by conjugating a bioactive motif from BMP-7 (RKPS) onto the C-terminal of the peptide RADARADARADARADA (RADA16-I) at a ratio of 1:1 to form a new RADARKPS peptide. Human nucleus pulposus-derived stem cells (NPDCs) were cultured in the presence of RADA-RKPS or RADA16-I in an apoptosis-promoting environment that was induced by tumor necrosis factor-alpha, and cells were cultured with RADA16-I in normal medium that served as the control group. After 48 h of apoptosis induction, the viability, proliferation, apoptosis rate, and expression of apoptosis-related genes of NPDCs in the different groups were evaluated, and the differentiation of NPDCs toward nucleus pulposus-like cells was tested. The results showed that the RADA-RKPS peptide could significantly protect the survival and proliferation of NPDCs. In addition, the application of RADA-RKPS decreased the rate of cell apoptosis, as detected by TUNEL-positive staining. Furthermore, our in vitro study confirmed the apoptosis-protecting effects of RADA-RKPS peptides, which significantly reduced the BAX/BCL-2 ratio of NPDCs and upregulated the gene expression of collagen II a1, aggrecan, and Sox-9 after 48 h of apoptosis induction. Collectively, these lines of evidence suggest that RADA-RKPS peptides confer a protective effect to NPDCs in an apoptosis environment, suggesting their potential application in the development of new biological treatment strategies for IVDD.
authors: 1 The Third Affiliated Hospital of Southern Medical University , Guangzhou, China .|2 Department of Orthopedic Surgery, Navy General Hospital , Beijing, People's Republic of China .|3 Department of Orthopedic Surgery, The People's Hospital of Gaozhou, Guangdong, People's Republic of China .
authors: Xiao-Chuan
authors: XC
authors: Li
authors: 2 Department of Orthopedic Surgery, Navy General Hospital , Beijing, People's Republic of China .
authors: Yao-Hong
authors: YH
authors: Wu
authors: 2 Department of Orthopedic Surgery, Navy General Hospital , Beijing, People's Republic of China .
authors: Xue-Dong
authors: XD
authors: Bai
authors: 2 Department of Orthopedic Surgery, Navy General Hospital , Beijing, People's Republic of China .
authors: Wei
authors: W
authors: Ji
authors: 2 Department of Orthopedic Surgery, Navy General Hospital , Beijing, People's Republic of China .
authors: Zi-Ming
authors: ZM
authors: Guo
authors: 2 Department of Orthopedic Surgery, Navy General Hospital , Beijing, People's Republic of China .
authors: Chao-Feng
authors: CF
authors: Wang
authors: 2 Department of Orthopedic Surgery, Navy General Hospital , Beijing, People's Republic of China .
authors: Qing
authors: Q
authors: He
authors: 1 The Third Affiliated Hospital of Southern Medical University , Guangzhou, China .|2 Department of Orthopedic Surgery, Navy General Hospital , Beijing, People's Republic of China .
authors: Di-Ke
authors: DK
authors: Ruan
mesh_terms: D053674:Aggrecans / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects*; D055419:Bone Morphogenetic Protein 7 / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D024043:Collagen Type II / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000378:metabolism; D055153:Stem Cell Niche / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D053674:Aggrecans; C494826:BAX protein, human; C000595707:BCL2 protein, human; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; C499177:COL2A1 protein, human; D024043:Collagen Type II; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D051028:bcl-2-Associated X Protein