G protein-coupled receptor 35 stimulation reduces osteoclast activity in primary human bone cells

Maria L Price; Rachael A Wyatt; Ana Crastin; Aqfan Jamaluddin; Rowan S Hardy; Morten Frost; Caroline M Gorvin

doi:10.1093/jbmrpl/ziaf131

G protein-coupled receptor 35 stimulation reduces osteoclast activity in primary human bone cells

Maria L Price, Rachael A Wyatt, Ana Crastin, Aqfan Jamaluddin, Rowan S Hardy, Morten Frost, Caroline M Gorvin^*

^*Corresponding author for this work

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Abstract

Lay Summary: Expression of G protein-coupled receptor 35 (GPR35) is reduced in osteoporosis and Gpr35-knockout mice have reduced bone mass. Here we showed stimulation of GPR35 activates Gi/o and G12/13 signaling pathways to reduce bone resorption in human osteoclasts. The anti-resorptive activity of GPR35 agonists was comparable to current osteoporosis drugs, denosumab and alendronic acid. Our findings demonstrate that GPR35 has an important inhibitory role in human osteoclast activity and have defined the signaling pathways that drive these processes. GPR35 represents a promising novel target to reduce osteoclast activity that could be exploited for osteoporosis treatments.

Original language	English
Article number	ziaf131
Number of pages	11
Journal	JBMR Plus
Volume	9
Issue number	10
Early online date	6 Aug 2025
DOIs	https://doi.org/10.1093/jbmrpl/ziaf131
Publication status	Published - Oct 2025

Keywords

osteoporosis
orphan GPCR
TRAP
bone resorption
G protein signaling

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10.1093/jbmrpl/ziaf131Licence: Creative Commons: Attribution (CC BY)

PriceM2025GproteinFinal published version, 1.76 MBLicence: Creative Commons: Attribution (CC BY)

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G protein-coupled receptor 35 (GPR35) stimulation reduces osteoclast activity in primary human bone cells
Price, M. L., Wyatt, R. A., Crastin, A., Jamaluddin, A., Hardy, R. S., Frost, M. & Gorvin, C. M., 25 Apr 2025, bioRxiv.
Research output: Working paper/Preprint › Preprint

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Deciphering the complexities in ghrelin receptor signalling to improve understanding of appetite regulation
Gorvin, C. (Principal Investigator)
The Wellcome Trust
1/08/22 → 31/07/27
Project: Research

Cite this

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title = "G protein-coupled receptor 35 stimulation reduces osteoclast activity in primary human bone cells",

abstract = "Lay Summary: Expression of G protein-coupled receptor 35 (GPR35) is reduced in osteoporosis and Gpr35-knockout mice have reduced bone mass. Here we showed stimulation of GPR35 activates Gi/o and G12/13 signaling pathways to reduce bone resorption in human osteoclasts. The anti-resorptive activity of GPR35 agonists was comparable to current osteoporosis drugs, denosumab and alendronic acid. Our findings demonstrate that GPR35 has an important inhibitory role in human osteoclast activity and have defined the signaling pathways that drive these processes. GPR35 represents a promising novel target to reduce osteoclast activity that could be exploited for osteoporosis treatments.",

keywords = "osteoporosis, orphan GPCR, TRAP, bone resorption, G protein signaling",

author = "Price, \{Maria L\} and Wyatt, \{Rachael A\} and Ana Crastin and Aqfan Jamaluddin and Hardy, \{Rowan S\} and Morten Frost and Gorvin, \{Caroline M\}",

year = "2025",

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doi = "10.1093/jbmrpl/ziaf131",

language = "English",

volume = "9",

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T1 - G protein-coupled receptor 35 stimulation reduces osteoclast activity in primary human bone cells

AU - Price, Maria L

AU - Wyatt, Rachael A

AU - Crastin, Ana

AU - Jamaluddin, Aqfan

AU - Hardy, Rowan S

AU - Frost, Morten

AU - Gorvin, Caroline M

PY - 2025/10

Y1 - 2025/10

N2 - Lay Summary: Expression of G protein-coupled receptor 35 (GPR35) is reduced in osteoporosis and Gpr35-knockout mice have reduced bone mass. Here we showed stimulation of GPR35 activates Gi/o and G12/13 signaling pathways to reduce bone resorption in human osteoclasts. The anti-resorptive activity of GPR35 agonists was comparable to current osteoporosis drugs, denosumab and alendronic acid. Our findings demonstrate that GPR35 has an important inhibitory role in human osteoclast activity and have defined the signaling pathways that drive these processes. GPR35 represents a promising novel target to reduce osteoclast activity that could be exploited for osteoporosis treatments.

AB - Lay Summary: Expression of G protein-coupled receptor 35 (GPR35) is reduced in osteoporosis and Gpr35-knockout mice have reduced bone mass. Here we showed stimulation of GPR35 activates Gi/o and G12/13 signaling pathways to reduce bone resorption in human osteoclasts. The anti-resorptive activity of GPR35 agonists was comparable to current osteoporosis drugs, denosumab and alendronic acid. Our findings demonstrate that GPR35 has an important inhibitory role in human osteoclast activity and have defined the signaling pathways that drive these processes. GPR35 represents a promising novel target to reduce osteoclast activity that could be exploited for osteoporosis treatments.

KW - osteoporosis

KW - orphan GPCR

KW - TRAP

KW - bone resorption

KW - G protein signaling

UR - https://www.scopus.com/pages/publications/105016330284

U2 - 10.1093/jbmrpl/ziaf131

DO - 10.1093/jbmrpl/ziaf131

M3 - Article

SN - 2473-4039

VL - 9

JO - JBMR Plus

JF - JBMR Plus

IS - 10

M1 - ziaf131

ER -

G protein-coupled receptor 35 stimulation reduces osteoclast activity in primary human bone cells

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G protein-coupled receptor 35 (GPR35) stimulation reduces osteoclast activity in primary human bone cells

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Deciphering the complexities in ghrelin receptor signalling to improve understanding of appetite regulation

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