Roles of Sodium Hydrogen Exchanger (NHE1) and Anion Exchanger (AE2) across Chondrocytes Plasma Membrane during Longitudinal Bone Growth

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<sup>+</sup>/H<sup>+</sup> (sodium hydrogen exchanger (NHE1)) and HCO&...

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Main Authors: Adamu Abdul Abubakar, Ahmed Khalaf Ali, Sahar Mohammed Ibrahim, Kareem Obayes Handool, Mohammad Shuaib Khan, Noordin Mohamed Mustapha, Tengku Azmi Tengku Ibrahim, Ubedullah Kaka, Loqman Mohamad Yusof
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Membranes
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Online Access:https://www.mdpi.com/2077-0375/12/7/707
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author Adamu Abdul Abubakar
Ahmed Khalaf Ali
Sahar Mohammed Ibrahim
Kareem Obayes Handool
Mohammad Shuaib Khan
Noordin Mohamed Mustapha
Tengku Azmi Tengku Ibrahim
Ubedullah Kaka
Loqman Mohamad Yusof
author_facet Adamu Abdul Abubakar
Ahmed Khalaf Ali
Sahar Mohammed Ibrahim
Kareem Obayes Handool
Mohammad Shuaib Khan
Noordin Mohamed Mustapha
Tengku Azmi Tengku Ibrahim
Ubedullah Kaka
Loqman Mohamad Yusof
author_sort Adamu Abdul Abubakar
collection DOAJ
description 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<sup>+</sup>/H<sup>+</sup> (sodium hydrogen exchanger (NHE1)) and HCO<sub>3</sub><sup>−</sup> (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 (<i>p</i> < 0.05) by approximately 11%. The inhibitor significantly (<i>p</i> < 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 (<i>p</i> < 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 (<i>p</i> < 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.
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spelling doaj.art-47e995d2b3df403f885d3d4f5d0a73fa2023-12-01T22:25:53ZengMDPI AGMembranes2077-03752022-07-0112770710.3390/membranes12070707Roles of Sodium Hydrogen Exchanger (NHE1) and Anion Exchanger (AE2) across Chondrocytes Plasma Membrane during Longitudinal Bone GrowthAdamu Abdul Abubakar0Ahmed Khalaf Ali1Sahar Mohammed Ibrahim2Kareem Obayes Handool3Mohammad Shuaib Khan4Noordin Mohamed Mustapha5Tengku Azmi Tengku Ibrahim6Ubedullah Kaka7Loqman Mohamad Yusof8Department of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, MalaysiaDepartment of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, MalaysiaDepartment of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, MalaysiaDepartment of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, MalaysiaDepartment of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, MalaysiaDepartment of Veterinary Pathology and Microbiology, Universiti Putra Malaysia, Serdang 43400, MalaysiaDepartment of Pre-Clinical Veterinary Sciences, Universiti Putra Malaysia, Serdang 43400, MalaysiaDepartment of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, MalaysiaDepartment of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang 43400, MalaysiaMammalian 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<sup>+</sup>/H<sup>+</sup> (sodium hydrogen exchanger (NHE1)) and HCO<sub>3</sub><sup>−</sup> (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 (<i>p</i> < 0.05) by approximately 11%. The inhibitor significantly (<i>p</i> < 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 (<i>p</i> < 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 (<i>p</i> < 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.https://www.mdpi.com/2077-0375/12/7/707long bone growthgrowth platechondrocytesplasma membrane inhibitors
spellingShingle Adamu Abdul Abubakar
Ahmed Khalaf Ali
Sahar Mohammed Ibrahim
Kareem Obayes Handool
Mohammad Shuaib Khan
Noordin Mohamed Mustapha
Tengku Azmi Tengku Ibrahim
Ubedullah Kaka
Loqman Mohamad Yusof
Roles of Sodium Hydrogen Exchanger (NHE1) and Anion Exchanger (AE2) across Chondrocytes Plasma Membrane during Longitudinal Bone Growth
Membranes
long bone growth
growth plate
chondrocytes
plasma membrane inhibitors
title Roles of Sodium Hydrogen Exchanger (NHE1) and Anion Exchanger (AE2) across Chondrocytes Plasma Membrane during Longitudinal Bone Growth
title_full Roles of Sodium Hydrogen Exchanger (NHE1) and Anion Exchanger (AE2) across Chondrocytes Plasma Membrane during Longitudinal Bone Growth
title_fullStr Roles of Sodium Hydrogen Exchanger (NHE1) and Anion Exchanger (AE2) across Chondrocytes Plasma Membrane during Longitudinal Bone Growth
title_full_unstemmed Roles of Sodium Hydrogen Exchanger (NHE1) and Anion Exchanger (AE2) across Chondrocytes Plasma Membrane during Longitudinal Bone Growth
title_short Roles of Sodium Hydrogen Exchanger (NHE1) and Anion Exchanger (AE2) across Chondrocytes Plasma Membrane during Longitudinal Bone Growth
title_sort roles of sodium hydrogen exchanger nhe1 and anion exchanger ae2 across chondrocytes plasma membrane during longitudinal bone growth
topic long bone growth
growth plate
chondrocytes
plasma membrane inhibitors
url https://www.mdpi.com/2077-0375/12/7/707
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