{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:19:42Z","timestamp":1780546782331,"version":"3.54.1"},"reference-count":101,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004515","name":"Universiti Kebangsaan Malaysia","doi-asserted-by":"publisher","award":["GUP-2017-032"],"award-info":[{"award-number":["GUP-2017-032"]}],"id":[{"id":"10.13039\/501100004515","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004515","name":"Universiti Kebangsaan Malaysia","doi-asserted-by":"publisher","award":["FF-2019-016"],"award-info":[{"award-number":["FF-2019-016"]}],"id":[{"id":"10.13039\/501100004515","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Faculty of Medicine, Universiti Kebangsaan Malaysia","award":["GUP-2017-032"],"award-info":[{"award-number":["GUP-2017-032"]}]},{"name":"The Faculty of Medicine, Universiti Kebangsaan Malaysia","award":["FF-2019-016"],"award-info":[{"award-number":["FF-2019-016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Changes in mitochondrial bioenergetics are believed to take place during osteoclastogenesis. This study aims to assess changes in mitochondrial bioenergetics and reactive oxygen species (ROS) levels during polyethylene (PE)-induced osteoclastogenesis in vitro. For this purpose, RAW264.7 cells were cultured for nine days and allowed to differentiate into osteoclasts in the presence of PE and RANKL. The total TRAP-positive cells, resorption activity, expression of osteoclast marker genes, ROS level, mitochondrial bioenergetics, glycolysis, and substrate utilization were measured. The effect of tocotrienols-rich fraction (TRF) treatment (50 ng\/mL) on those parameters during PE-induced osteoclastogenesis was also studied. During PE-induced osteoclastogenesis, as depicted by an increase in TRAP-positive cells and gene expression of osteoclast-related markers, higher proton leak, higher extracellular acidification rate (ECAR), as well as higher levels of ROS and NADPH oxidases (NOXs) were observed in the differentiated cells. The oxidation level of some substrates in the differentiated group was higher than in other groups. TRF treatment significantly reduced the number of TRAP-positive osteoclasts, bone resorption activity, and ROS levels, as well as modulating the gene expression of antioxidant-related genes and mitochondrial function. In conclusion, changes in mitochondrial bioenergetics and substrate utilization were observed during PE-induced osteoclastogenesis, while TRF treatment modulated these changes.<\/jats:p>","DOI":"10.3390\/ijms23158331","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T20:49:28Z","timestamp":1659041368000},"page":"8331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Changes in Metabolism and Mitochondrial Bioenergetics during Polyethylene-Induced Osteoclastogenesis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7814-7761","authenticated-orcid":false,"given":"Nur Shukriyah","family":"Mohamad Hazir","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia"},{"name":"Clinical Laboratory Section, Institute of Medical Science Technology, Universiti Kuala Lumpur, A1-1, Jalan TKS 1, Taman Kajang Sentral, Kajang 43000, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nor Hamdan Mohamad","family":"Yahaya","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Faculty of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-4782","authenticated-orcid":false,"given":"Muhamad Syahrul Fitri","family":"Zawawi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6948-8839","authenticated-orcid":false,"given":"Hanafi Ahmad","family":"Damanhuri","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2480-0224","authenticated-orcid":false,"given":"Norazlina","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0326-977X","authenticated-orcid":false,"given":"Ekram","family":"Alias","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1111\/febs.14142","article-title":"Novel RANKL DE-loop mutants antagonize RANK-mediated osteoclastogenesis","volume":"284","author":"Wang","year":"2017","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0092-8674(00)80209-3","article-title":"Osteoprotegerin: A novel secreted protein involved in the regulation of bone density","volume":"89","author":"Simonet","year":"1997","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1084\/jem.190.12.1741","article-title":"Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors","volume":"190","author":"Arai","year":"1999","journal-title":"J. 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