TRPV4 regulates osteoblast differentiation and mitochondrial function that are relevant for channelopathy

Tusar Kanta Acharya; Subhashis Pal; Arijit Ghosh; Shamit Kumar; Satish Kumar; Naibedya Chattopadhyay; Chandan Goswami

doi:10.3389/fcell.2023.1066788

TRPV4 regulates osteoblast differentiation and mitochondrial function that are relevant for channelopathy

Front Cell Dev Biol. 2023 Jun 12:11:1066788. doi: 10.3389/fcell.2023.1066788. eCollection 2023.

Authors

Tusar Kanta Acharya^{1

2}, Subhashis Pal³, Arijit Ghosh^{1

2}, Shamit Kumar^{1

2}, Satish Kumar¹, Naibedya Chattopadhyay^{3

4}, Chandan Goswami^{1

2}

Affiliations

¹ National Institute of Science Education and Research, HBNI, School of Biological Sciences, Bhubaneswar, Odisha, India.
² Training School Complex, Homi Bhabha National Institute, Mumbai, India.
³ Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), Central Drug Research Institute (CDRI), Council of Scientific and Industrial Research (CSIR), Lucknow, India.
⁴ AcSIR, CSIR-Central Drug Research Institute Campus, Lucknow, India.

Abstract

Different ion channels present in the osteoblast regulate the cellular functions including bio-mineralization, a process that is a highly stochastic event. Cellular events and molecular signaling involved in such process is poorly understood. Here we demonstrate that TRPV4, a mechanosensitive ion channel is endogenously present in an osteoblast cell line (MC3T3-E1) and in primary osteoblasts. Pharmacological activation of TRPV4 enhanced intracellular Ca²⁺-level, expression of osteoblast-specific genes and caused increased bio-mineralization. TRPV4 activation also affects mitochondrial Ca²⁺-levels and mitochondrial metabolisms. We further demonstrate that different point mutants of TRPV4 induce different mitochondrial morphology and have different levels of mitochondrial translocation, collectively suggesting that TRPV4-mutation-induced bone disorders and other channelopathies are mostly due to mitochondrial abnormalities. These findings may have broad biomedical implications.

Keywords: bio-mineralization; bone; channelopathy; genetic disorder; mitochondria.

Grants and funding

CG acknowledges funding from NISER and DBT (Govt. India, grant number BT/PR8004/MED/30/988/2013). CG and all the authors acknowledge all the present and former lab members for supporting this work.