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Bone & Joint Research
Vol. 11, Issue 12 | Pages 854 - 861
1 Dec 2022
Park TJ Park SY Cho W Oh H Lee HJ Abd El-Aty AM Bayram C Jeong JH Jung TW

Aims. Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear. Methods. Human primary tenocytes were cultured in palmitate (400 μM) and palmitate plus DEL-1 (0 to 2 μg/ml) conditions for 24 hours. The expression levels of ER stress markers and cleaved caspase 3, as well as phosphorylated 5' adenosine monophosphate-activated protein kinase (AMPK) and autophagy markers, were assessed by Western blotting. Autophagosome formation was measured by staining with monodansylcadaverine, and apoptosis was determined by cell viability assay and caspase 3 activity assay. Results. We found that treatment with DEL-1 suppressed palmitate-induced inflammation, ER stress, and apoptosis in human primary tenocytes. DEL-1 treatment augmented LC3 conversion and p62 degradation as well as AMPK phosphorylation. Moreover, small interfering RNA for AMPK or 3-methyladenine (3-MA), an autophagy inhibitor, abolished the suppressive effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes. Similar to DEL-1, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, also attenuated palmitate-induced inflammation, ER stress, and apoptosis in tenocytes, which 3-MA reversed. Conclusion. These results revealed that DEL-1 suppresses inflammation and ER stress, thereby attenuating tenocyte apoptosis through AMPK/autophagy-mediated signalling. Thus, regular exercise or administration of DEL-1 may directly contribute to improving tendinitis exacerbated by obesity and insulin resistance. Cite this article: Bone Joint Res 2022;11(12):854–861


The Bone & Joint Journal
Vol. 97-B, Issue 8 | Pages 1126 - 1131
1 Aug 2015
Nortunen S Flinkkilä T Lantto I Kortekangas T Niinimäki J Ohtonen P Pakarinen H

We prospectively assessed the diagnostic accuracy of the gravity stress test and clinical findings to evaluate the stability of the ankle mortise in patients with supination–external rotation-type fractures of the lateral malleolus without widening of the medial clear space. The cohort included 79 patients with a mean age of 44 years (16 to 82). Two surgeons assessed medial tenderness, swelling and ecchymosis and performed the external rotation (ER) stress test (a reference standard). A diagnostic radiographer performed the gravity stress test. For the gravity stress test, the positive likelihood ratio (LR) was 5.80 with a 95% confidence interval (CI) of 2.75 to 12.27, and the negative LR was 0.15 (95% CI 0.07 to 0.35), suggesting a moderate change from the pre-test probability. Medial tenderness, both alone and in combination with swelling and/or ecchymosis, indicated a small change (positive LR, 2.74 to 3.25; negative LR, 0.38 to 0.47), whereas swelling and ecchymosis indicated only minimal changes (positive LR, 1.41 to 1.65; negative LR, 0.38 to 0.47). . In conclusion, when gravity stress test results are in agreement with clinical findings, the result is likely to predict stability of the ankle mortise with an accuracy equivalent to ER stress test results. When clinical examination suggests a medial-side injury, however, the gravity stress test may give a false negative result. Cite this article: Bone Joint J 2015; 97-B:1126–31


Bone & Joint Research
Vol. 9, Issue 11 | Pages 827 - 839
1 Nov 2020
Hameister R Lohmann CH Dheen ST Singh G Kaur C

Aims

This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss.

Methods

TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA).