PMID- 29992506 OWN - NLM STAT- MEDLINE DCOM- 20190102 LR - 20190102 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 41 IP - 5 DP - 2018 Oct TI - Progranulin Is Positively Associated with Intervertebral Disc Degeneration by Interaction with IL-10 and IL-17 Through TNF Pathways. PG - 1852-1863 LID - 10.1007/s10753-018-0828-1 [doi] AB - Progranulin (PGRN) is a widely expressed growth factor that effectively inhibits tumor necrosis factor alpha (TNFalpha)-mediated inflammatory response. TNFalpha is involved in intervertebral disc degeneration (IDD) and plays a key role. This study aims to determine the role of PGRN in the intervertebral disc degeneration process. We collected intervertebral discs (IVDs) from humans and mice with different genetic backgrounds. We examined the expression of PGRN in IVD tissues by immunohistochemistry staining and Western blotting assay. We examined the peripheral serum level of PGRN by ELISA assay. Murine IVD tissue samples were taken to undergo safranin O, HE, and immunohistochemistry staining. Primary human nucleus pulposus cells were used for ELISA and RT-PCR assays. PGRN as well as interlukin-10 (IL-10) and interlukin-17 (IL-17) expressions were elevated in degenerative discs and peripheral blood sera. Loss of PGRN led to accelerated disc degeneration in the animal model, along with decreased expression of IL-10 and increased expression of IL-17. Additionally, the PGRN level was positively related to levels of IL-10 and IL-17. In vitro study suggested that PGRN protected against disc degeneration by inducing IL-10 and reducing IL-17. PGRN is associated with intervertebral disc degeneration through interfering with IL-10 and IL-17; thus, PGRN could be an interesting biomarker for diagnosis and a potential treatment target. FAU - Wang, Shaoyi AU - Wang S AD - Department of Orthopaedics, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. AD - School of Medicine, Shandong University, Jinan, China. FAU - Wei, Jianlu AU - Wei J AD - Department of Orthopaedics, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. FAU - Fan, Yuchen AU - Fan Y AD - School of Medicine, Shandong University, Jinan, China. FAU - Ding, Hong AU - Ding H AD - Department of Orthopaedics, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. AD - School of Medicine, Shandong University, Jinan, China. FAU - Tian, Huichao AU - Tian H AD - Department of Orthopaedics, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. AD - School of Medicine, Shandong University, Jinan, China. FAU - Zhou, Xiaocong AU - Zhou X AD - School of Medicine, Shandong University, Jinan, China. FAU - Cheng, Lei AU - Cheng L AD - Department of Orthopaedics, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. chengleiyx@126.com. LA - eng GR - 81572191/National Natural Science Foundation of China/ PT - Journal Article PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Interleukin-17) RN - 0 (Progranulins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Humans MH - Interleukin-10/*metabolism MH - Interleukin-17/*metabolism MH - Intervertebral Disc/metabolism/pathology MH - Intervertebral Disc Degeneration/diagnosis/*metabolism MH - Mice MH - Progranulins/*analysis MH - Tumor Necrosis Factor-alpha/*metabolism OTO - NOTNLM OT - IL-10 OT - IL-17 OT - TNFalpha OT - intervertebral disc degeneration OT - progranulin EDAT- 2018/07/12 06:00 MHDA- 2019/01/03 06:00 CRDT- 2018/07/12 06:00 PHST- 2018/07/12 06:00 [pubmed] PHST- 2019/01/03 06:00 [medline] PHST- 2018/07/12 06:00 [entrez] AID - 10.1007/s10753-018-0828-1 [pii] AID - 10.1007/s10753-018-0828-1 [doi] PST - ppublish SO - Inflammation. 2018 Oct;41(5):1852-1863. doi: 10.1007/s10753-018-0828-1.