An Optogenetic Approach for Regulating Human Parathyroid Hormone Secretion

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Feb 10

PMID 35140213

Authors

Yunhui Liu

Lu Zhang

Nan Hu

Jie Shao

Dazhi Yang

Changshun Ruan

Shishu Huang

Liping Wang

William W Lu

Xinzhou Zhang

Fan Yang

Affiliations

Soon will be listed here.

Abstract

Parathyroid hormone (PTH) plays crucial role in maintaining calcium and phosphorus homeostasis. In the progression of secondary hyperparathyroidism (SHPT), expression of calcium-sensing receptors (CaSR) in the parathyroid gland decreases, which leads to persistent hypersecretion of PTH. How to precisely manipulate PTH secretion in parathyroid tissue and underlying molecular mechanism is not clear. Here, we establish an optogenetic approach that bypasses CaSR to inhibit PTH secretion in human hyperplastic parathyroid cells. We found that optogenetic stimulation elevates intracellular calcium, inhibits both PTH synthesis and secretion in human parathyroid cells. Long-term pulsatile PTH secretion induced by light stimulation prevented hyperplastic parathyroid tissue-induced bone loss by influencing the bone remodeling in mice. The effects are mediated by light stimulation of opsin expressing parathyroid cells and other type of cells in parathyroid tissue. Our study provides a strategy to regulate release of PTH and associated bone loss of SHPT through an optogenetic approach.

Citing Articles

A sensitive red/far-red photoswitch for controllable gene therapy in mouse models of metabolic diseases.

Qiao L, Niu L, Wang M, Wang Z, Kong D, Yu G Nat Commun. 2024; 15(1):10310.

PMID: 39604418 PMC: 11603164. DOI: 10.1038/s41467-024-54781-2.

Frontiers and future perspectives of neuroimmunology.

Qi H, Duan S, Xu Y, Zhang H Fundam Res. 2024; 4(2):206-217.

PMID: 38933499 PMC: 11197808. DOI: 10.1016/j.fmre.2022.10.002.

Editorial: Parathyroid disorders: updates of PTH/serum Ca2+ regulation and therapeutic prospects.

Zhang F, Huang Y, Hu J, Yin S Front Endocrinol (Lausanne). 2024; 14:1354277.

PMID: 38292765 PMC: 10826605. DOI: 10.3389/fendo.2023.1354277.

LITTIP/Lgr6/HnRNPK complex regulates cementogenesis via Wnt signaling.

Li T, Wang H, Jiang Y, Chen S, Huang D, Wu Z Int J Oral Sci. 2023; 15(1):33.

PMID: 37558690 PMC: 10412570. DOI: 10.1038/s41368-023-00237-0.

Potential effects of teriparatide (PTH (1-34)) on osteoarthritis: a systematic review.

Li G, Liu S, Xu H, Chen Y, Deng J, Xiong A Arthritis Res Ther. 2023; 25(1):3.

PMID: 36609338 PMC: 9817404. DOI: 10.1186/s13075-022-02981-w.

References

Conigrave A . The Calcium-Sensing Receptor and the Parathyroid: Past, Present, Future. Front Physiol. 2016; 7:563. PMC: 5156698. DOI: 10.3389/fphys.2016.00563. View

Lee N, Sowa H, Hinoi E, Ferron M, Ahn J, Confavreux C . Endocrine regulation of energy metabolism by the skeleton. Cell. 2007; 130(3):456-69. PMC: 2013746. DOI: 10.1016/j.cell.2007.05.047. View

Fraser W . Hyperparathyroidism. Lancet. 2009; 374(9684):145-58. DOI: 10.1016/S0140-6736(09)60507-9. View

Silverberg S, Shane E, De La Cruz L, Dempster D, Feldman F, Seldin D . Skeletal disease in primary hyperparathyroidism. J Bone Miner Res. 1989; 4(3):283-91. DOI: 10.1002/jbmr.5650040302. View

Bilezikian J, Cusano N, Khan A, Liu J, Marcocci C, Bandeira F . Primary hyperparathyroidism. Nat Rev Dis Primers. 2016; 2:16033. PMC: 5385896. DOI: 10.1038/nrdp.2016.33. View

Hannan F, Kallay E, Chang W, Brandi M, Thakker R . The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases. Nat Rev Endocrinol. 2018; 15(1):33-51. PMC: 6535143. DOI: 10.1038/s41574-018-0115-0. View

Schmitt C, Locken S, Mehls O, Veldhuis J, Lehnert T, Ritz E . PTH pulsatility but not calcium sensitivity is restored after total parathyroidectomy with heterotopic autotransplantation. J Am Soc Nephrol. 2003; 14(2):407-14. DOI: 10.1097/01.asn.0000043905.35268.86. View

Gardinier J, Al-Omaishi S, Rostami N, Morris M, Kohn D . Examining the influence of PTH(1-34) on tissue strength and composition. Bone. 2018; 117:130-137. PMC: 6202137. DOI: 10.1016/j.bone.2018.09.019. View

Ono T, Nakashima T . Recent advances in osteoclast biology. Histochem Cell Biol. 2018; 149(4):325-341. DOI: 10.1007/s00418-018-1636-2. View

10.

Suarez-Bregua P, Cal L, Canestro C, Rotllant J . PTH Reloaded: A New Evolutionary Perspective. Front Physiol. 2017; 8:776. PMC: 5640766. DOI: 10.3389/fphys.2017.00776. View

11.

Mickle A, Won S, Noh K, Yoon J, Meacham K, Xue Y . A wireless closed-loop system for optogenetic peripheral neuromodulation. Nature. 2019; 565(7739):361-365. PMC: 6336505. DOI: 10.1038/s41586-018-0823-6. View

12.

Li J, Xiao Z, Hu X, Li Y, Zhang X, Zhang S . Total parathyroidectomy with forearm auto-transplantation improves the quality of life and reduces the recurrence of secondary hyperparathyroidism in chronic kidney disease patients. Medicine (Baltimore). 2017; 96(49):e9050. PMC: 5728923. DOI: 10.1097/MD.0000000000009050. View

13.

Campos P, Herbison A . Optogenetic activation of GnRH neurons reveals minimal requirements for pulsatile luteinizing hormone secretion. Proc Natl Acad Sci U S A. 2014; 111(51):18387-92. PMC: 4280623. DOI: 10.1073/pnas.1415226112. View

14.

Wein M, Kronenberg H . Regulation of Bone Remodeling by Parathyroid Hormone. Cold Spring Harb Perspect Med. 2018; 8(8). PMC: 6071549. DOI: 10.1101/cshperspect.a031237. View

15.

Rodriguez M, Nemeth E, Martin D . The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism. Am J Physiol Renal Physiol. 2004; 288(2):F253-64. DOI: 10.1152/ajprenal.00302.2004. View

16.

Hibi Y, Kambe F, Imai T, Ogawa K, Shimizu Y, Shibata M . Increased protein kinase A type Iα regulatory subunit expression in parathyroid gland adenomas of patients with primary hyperparathyroidism. Endocr J. 2012; 60(2):215-23. DOI: 10.1507/endocrj.ej12-0267. View

17.

Canalejo A, Canalejo R, Rodriguez M, Martinez-Moreno J, Felsenfeld A, Rodriguez M . Development of parathyroid gland hyperplasia without uremia: role of dietary calcium and phosphate. Nephrol Dial Transplant. 2009; 25(4):1087-97. DOI: 10.1093/ndt/gfp616. View

18.

Riccardi D, Brown E . Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol. 2009; 298(3):F485-99. PMC: 2838589. DOI: 10.1152/ajprenal.00608.2009. View

19.

Pathak P, Holden S, Schaefer S, Leverson G, Chen H, Sippel R . Elevated parathyroid hormone after parathyroidectomy delays symptom improvement. J Surg Res. 2014; 190(1):119-25. PMC: 4143245. DOI: 10.1016/j.jss.2014.02.050. View

20.

Bajwa N, Sanchez C, Lindsey R, Watt H, Mohan S . Cortical and trabecular bone are equally affected in rats with renal failure and secondary hyperparathyroidism. BMC Nephrol. 2018; 19(1):24. PMC: 5796449. DOI: 10.1186/s12882-018-0822-8. View