The intricate mechanism of PLS3 in bone homeostasis and disease

Wenchao Zhong; Janak L Pathak; Yueting Liang; Lidiia Zhytnik; Gerard Pals; Elisabeth M W Eekhoff; Nathalie Bravenboer; Dimitra Micha

doi:10.3389/fendo.2023.1168306

The intricate mechanism of PLS3 in bone homeostasis and disease

Front Endocrinol (Lausanne). 2023 Jul 7:14:1168306. doi: 10.3389/fendo.2023.1168306. eCollection 2023.

Authors

Wenchao Zhong^{1

2

3

4}, Janak L Pathak⁴, Yueting Liang^{5

6}, Lidiia Zhytnik^{1

3

7}, Gerard Pals^{1

3}, Elisabeth M W Eekhoff^{8

9}, Nathalie Bravenboer^{2

3}, Dimitra Micha^{1

3

9}

Affiliations

¹ Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
² Department of Clinical Chemistry, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
³ Amsterdam Movement Sciences, Tissue Function And Regeneration, Amsterdam, Netherlands.
⁴ Department of Temporomandibular Joint, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
⁵ Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
⁶ The Second Clinical College, Guangzhou Medical University, Guangzhou, China.
⁷ Department of Traumatology and Orthopaedics, Institute of Clinical Medicine, The University of Tartu, Tartu, Estonia.
⁸ Department Internal Medicine Section Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit Amsterdam, Rare Bone Disease Center, AMS, Amsterdam, Netherlands.
⁹ Amsterdam Reproduction and Development Research Institute, Amsterdam, Netherlands.

Abstract

Since our discovery in 2013 that genetic defects in PLS3 lead to bone fragility, the mechanistic details of this process have remained obscure. It has been established that PLS3 variants cause syndromic and nonsyndromic osteoporosis as well as osteoarthritis. PLS3 codes for an actin-bundling protein with a broad pattern of expression. As such, it is puzzling how PLS3 specifically leads to bone-related disease presentation. Our review aims to summarize the current state of knowledge regarding the function of PLS3 in the predominant cell types in the bone tissue, the osteocytes, osteoblasts and osteoclasts. This is related to the role of PLS3 in regulating mechanotransduction, calcium regulation, vesicle trafficking, cell differentiation and mineralization as part of the complex bone pathology presented by PLS3 defects. Considering the consequences of PLS3 defects on multiple aspects of bone tissue metabolism, our review motivates the study of its mechanism in bone diseases which can potentially help in the design of suitable therapy.

Keywords: PLS3; bone cells; bone diseases; calcium regulation; mechanotransduction; osteogenesis.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Bone and Bones / pathology
Homeostasis
Humans
Mechanotransduction, Cellular*
Mutation
Osteoporosis* / pathology

Grants and funding

The work of WZ is funded by the Guangzhou Elites Scholarship Council PhD scholarship. The work of LZ is supported by the Estonian Research Council, grant PUTJD1009.