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:https://doi.org/10.3389/fendo.2023.1168306

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

Research output: Contribution to journal › Review article › Academic › peer-review

1 Citation (Scopus)

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.

Original language	English
Article number	1168306
Journal	Frontiers in Endocrinology
Volume	14
DOIs	https://doi.org/10.3389/fendo.2023.1168306
Publication status	Published - 2023

Keywords

PLS3
bone cells
bone diseases
calcium regulation
mechanotransduction
osteogenesis

Access to Document

https://doi.org/10.3389/fendo.2023.1168306

Cite this

@article{072773fc3f544b90a97a11d333c058cf,

title = "The intricate mechanism of PLS3 in bone homeostasis and disease",

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",

author = "Wenchao Zhong and Pathak, {Janak L.} and Yueting Liang and Lidiia Zhytnik and Gerard Pals and Eekhoff, {Elisabeth M. W.} and Nathalie Bravenboer and Dimitra Micha",

note = "Funding Information: 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. Acknowledgments Publisher Copyright: Copyright {\textcopyright} 2023 Zhong, Pathak, Liang, Zhytnik, Pals, Eekhoff, Bravenboer and Micha.",

year = "2023",

doi = "https://doi.org/10.3389/fendo.2023.1168306",

language = "English",

volume = "14",

journal = "Frontiers in Endocrinology",

issn = "1664-2392",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - The intricate mechanism of PLS3 in bone homeostasis and disease

AU - Zhong, Wenchao

AU - Pathak, Janak L.

AU - Liang, Yueting

AU - Zhytnik, Lidiia

AU - Pals, Gerard

AU - Eekhoff, Elisabeth M. W.

AU - Bravenboer, Nathalie

AU - Micha, Dimitra

N1 - Funding Information: 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. Acknowledgments Publisher Copyright: Copyright © 2023 Zhong, Pathak, Liang, Zhytnik, Pals, Eekhoff, Bravenboer and Micha.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - PLS3

KW - bone cells

KW - bone diseases

KW - calcium regulation

KW - mechanotransduction

KW - osteogenesis

UR - http://www.scopus.com/inward/record.url?scp=85165254104&partnerID=8YFLogxK

U2 - https://doi.org/10.3389/fendo.2023.1168306

DO - https://doi.org/10.3389/fendo.2023.1168306

M3 - Review article

C2 - 37484945

SN - 1664-2392

VL - 14

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

M1 - 1168306

ER -

The intricate mechanism of PLS3 in bone homeostasis and disease

Abstract

Keywords

Access to Document

Other files and links

Cite this