{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T02:45:32Z","timestamp":1774579532673,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T00:00:00Z","timestamp":1587427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 107-2314-B-182A-036-MY3"],"award-info":[{"award-number":["MOST 107-2314-B-182A-036-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2320-B-182A-020 -MY3"],"award-info":[{"award-number":["MOST 108-2320-B-182A-020 -MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3H1311"],"award-info":[{"award-number":["CMRPG3H1311"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3H1381"],"award-info":[{"award-number":["CMRPG3H1381"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Because of lipopolysaccharide (LPS)-mediated effects on osteoclast differentiation and bone loss, periprosthetic joint infection (PJI) caused by Gram-negative bacteria increases the risk of aseptic loosening after reimplantation. Synovial fluid interleukin-16 (IL-16) expression was higher in patients with PJI than in patients without joint infection. Thus, we explored the effects of IL-16 on bone. We investigated whether IL-16 modulates osteoclast or osteoblast differentiation in vitro. An LPS-induced bone loss mice model was used to explore the possible advantages of IL-16 inhibition for the prevention of bone loss. IL-16 directly activated p38 and c-Jun N-terminal kinase (JNK)\/mitogen-activated protein kinase (MAPK) signaling and increased osteoclast activation markers, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, and nuclear factor of activated T cells 1 (NFATc1). IL-16 directly caused monocytes to differentiate into TRAP-positive osteoclast-like cells through NFATc1 activation dependent on JNK\/MAPK signaling. Moreover, IL-16 did not alter alkaline phosphatase activity or calcium deposition during osteoblastic differentiation. Finally, IL-16 inhibition prevented LPS-induced trabecular bone loss and osteoclast activation in vivo. IL-16 directly increased osteoclast activation through the JNK\/NFATc1 pathway. IL-16 inhibition could represent a new strategy for treating infection-associated bone loss.<\/jats:p>","DOI":"10.3390\/ijms21082904","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T04:15:13Z","timestamp":1587528913000},"page":"2904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK\/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection"],"prefix":"10.3390","volume":"21","author":[{"given":"Yuhan","family":"Chang","sequence":"first","affiliation":[{"name":"Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1817-0302","authenticated-orcid":false,"given":"Yi-min","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Chien","family":"Hu","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Hsiang","family":"Chang","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cai-Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve W. N.","family":"Ueng","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"ref_1","first-page":"8","article-title":"The challenge of the increasing demand for joint replacement","volume":"129","author":"Hooper","year":"2016","journal-title":"N. Z. Med. 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