PMID- 35842459 OWN - NLM STAT- MEDLINE DCOM- 20220719 LR - 20220923 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 12 IP - 1 DP - 2022 Jul 16 TI - Reduced dynamic loads due to hip dislocation induce acetabular cartilage degeneration by IL-6 and MMP3 via the STAT3/periostin/NF-kappaB axis. PG - 12207 LID - 10.1038/s41598-022-16585-6 [doi] LID - 12207 AB - Developmental dysplasia of the hip (DDH) is characterized by anatomical abnormalities of the hip joint, ranging from mild acetabular dysplasia to hip subluxation and eventually dislocation. The mechanism underlying the cartilage degeneration of the hip joints exposed to reduced dynamic loads due to hip dislocation remains unknown. We established a rodent hip dislocation (disarticulation; DA) model of DDH (DA-DDH rats and mice) by swaddling. Expression levels of periostin (Postn) and catabolic factors, such as interleukin-6 (IL-6) and matrix metalloproteinase 3 (Mmp3), increased and those of chondrogenic markers decreased in the acetabular cartilage of the DA-DDH models. Postn induced IL-6 and Mmp3 expression in chondrocytes through integrin alphaVbeta3, focal adhesion kinase, Src, and nuclear factor-kappaB (NF-kappaB) signaling. The microgravity environment created by a random positioning machine induced Postn expression in chondrocytes through signal transducer and activator of transcription 3 (STAT3) signaling. IL-6 stimulated Postn expression via STAT3 signaling. Furthermore, cartilage degeneration was suppressed in the acetabulum of Postn(-/-) DA-DDH mice compared with that in the acetabulum of wild type DA-DDH mice. In summary, reduced dynamic loads due to hip dislocation induced acetabular cartilage degeneration via IL-6 and MMP3 through STAT3/periostin/NF-kappaB signaling in the rodent DA-DDH models. CI - (c) 2022. The Author(s). FAU - Nakamura, Yutaka AU - Nakamura Y AD - Department of Orthopaedic Surgery, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan. FAU - Saitou, Mitsuru AU - Saitou M AD - Department of Orthopaedic Surgery, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan. FAU - Komura, Shingo AU - Komura S AD - Department of Orthopaedic Surgery, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan. FAU - Matsumoto, Kazu AU - Matsumoto K AD - Department of Orthopaedic Surgery, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan. FAU - Ogawa, Hiroyasu AU - Ogawa H AD - Department of Orthopaedic Surgery, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan. FAU - Miyagawa, Takaki AU - Miyagawa T AD - Department of Orthopaedic Surgery, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan. FAU - Saitou, Takashi AU - Saitou T AD - Department of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Toon, Ehime, 791-0295, Japan. FAU - Imamura, Takeshi AU - Imamura T AD - Department of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Toon, Ehime, 791-0295, Japan. FAU - Imai, Yuuki AU - Imai Y AD - Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Toon, Ehime, 791-0295, Japan. FAU - Takayanagi, Hiroshi AU - Takayanagi H AD - Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan. FAU - Akiyama, Haruhiko AU - Akiyama H AD - Department of Orthopaedic Surgery, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan. hakiyama@gifu-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220716 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Interleukin-6) RN - 0 (NF-kappa B) RN - 0 (STAT3 Transcription Factor) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.17 (Mmp3 protein, mouse) SB - IM MH - Acetabulum MH - Animals MH - Cartilage MH - *Cartilage Diseases MH - *Hip Dislocation MH - Interleukin-6 MH - Matrix Metalloproteinase 3/genetics MH - Mice MH - NF-kappa B MH - Rats MH - STAT3 Transcription Factor PMC - PMC9288549 COIS- The authors declare no competing interests. EDAT- 2022/07/17 06:00 MHDA- 2022/07/20 06:00 PMCR- 2022/07/16 CRDT- 2022/07/16 23:17 PHST- 2022/04/12 00:00 [received] PHST- 2022/07/12 00:00 [accepted] PHST- 2022/07/16 23:17 [entrez] PHST- 2022/07/17 06:00 [pubmed] PHST- 2022/07/20 06:00 [medline] PHST- 2022/07/16 00:00 [pmc-release] AID - 10.1038/s41598-022-16585-6 [pii] AID - 16585 [pii] AID - 10.1038/s41598-022-16585-6 [doi] PST - epublish SO - Sci Rep. 2022 Jul 16;12(1):12207. doi: 10.1038/s41598-022-16585-6.