{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:35:16Z","timestamp":1790494516171,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education Malaysia Fundamental Research Grand","doi-asserted-by":"publisher","award":["02-01-13-1200FR"],"award-info":[{"award-number":["02-01-13-1200FR"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>Mammalian long bone growth occurs through endochondral ossification, majorly regulated by the controlled enlargement of chondrocytes at the growth plate (GP). This study aimed to investigate the roles of Na+\/H+ (sodium hydrogen exchanger (NHE1)) and HCO3\u2212 (anion exchanger [AE2]) during longitudinal bone growth in mammals. Bones from P10 SpragueDawley rat pups were cultured exvivo in the presence or absence of NHE1 and AE2 inhibitors to determine their effect on long bone growth. Gross morphometry, histomorphometry, and immunohistochemistry were used to assess the bone growth. The results revealed that the culture of the bones in the presence of NHE1 and AE2 inhibitors reduces bone growth significantly (p &lt; 0.05) by approximately 11%. The inhibitor significantly (p &lt; 0.05) reduces bone growth velocity and the length of the hypertrophic chondrocyte zone without any effect on the total GP length. The total GP chondrocyte density was significantly (p &lt; 0.05) reduced, but hypertrophic chondrocyte densities remained constant. NHE1 fluorescence signaling across the GP length was higher than AE2, and their localization was significantly (p &lt; 0.05) inhibited at the hypertrophic chondrocytes zone. The GP lengthening was majorly driven by an increase in the overall GP chondrocyte and hypertrophic chondrocyte densities apart from the regulatory volume phenomenon. This may suggest that NHE1 and AE2 could have a regulatory role in long bone growth.<\/jats:p>","DOI":"10.3390\/membranes12070707","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T01:57:11Z","timestamp":1657850231000},"page":"707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Roles of Sodium Hydrogen Exchanger (NHE1) and Anion Exchanger (AE2) across Chondrocytes Plasma Membrane during Longitudinal Bone Growth"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8643-4413","authenticated-orcid":false,"given":"Adamu Abdul","family":"Abubakar","sequence":"first","affiliation":[{"name":"Department of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, Malaysia"},{"name":"Department of Veterinary Surgery and Radiology, Usmanu Danfodiyo University, Sokoto PMB 2346, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Khalaf","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, Malaysia"},{"name":"Department of Surgery and Theriogenology, College of Veterinary Medicine, University of Mosul, Mosul 00964, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar Mohammed","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, Malaysia"},{"name":"Department of Surgery and Theriogenology, College of Veterinary Medicine, University of Mosul, Mosul 00964, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kareem Obayes","family":"Handool","sequence":"additional","affiliation":[{"name":"Department of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-1643","authenticated-orcid":false,"given":"Mohammad Shuaib","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, Malaysia"},{"name":"Faculty of Veterinary and Animal Science, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noordin Mohamed","family":"Mustapha","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology and Microbiology, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengku Azmi Tengku","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pre-Clinical Veterinary Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6469-3542","authenticated-orcid":false,"given":"Ubedullah","family":"Kaka","sequence":"additional","affiliation":[{"name":"Department of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loqman Mohamad","family":"Yusof","sequence":"additional","affiliation":[{"name":"Department of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.biocel.2007.06.009","article-title":"Endochondral ossification: How cartilage is converted into bone in the developing skeleton","volume":"40","author":"Mackie","year":"2008","journal-title":"Int. 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