Versatility of 14-3-3 Proteins and Their Roles in Bone and Joint-related Diseases

Overview

Journal Bone Res

Specialties Endocrinology
Orthopedics

Date 2024 Oct 15

PMID 39406741

Authors

Renpeng Zhou

Weirong Hu

Peter X Ma

Chuan-Ju Liu

Affiliations

Soon will be listed here.

Abstract

Bone and joint-related diseases, including osteoarthritis (OA), rheumatoid arthritis (RA), and bone tumors, pose significant health challenges due to their debilitating effects on the musculoskeletal system. 14-3-3 proteins, a family of conserved regulatory molecules, play a critical role in the pathology of these diseases. This review discusses the intricate structure and multifunctionality of 14-3-3 proteins, their regulation of signaling pathways, and their interactions with other proteins. We underscore the significance of 14-3-3 proteins in the regulation of osteoblasts, osteoclasts, chondrocytes, and bone remodeling, all key factors in the maintenance and dysfunction of bone and joint systems. Specific focus is directed toward elucidating the contribution of 14-3-3 proteins in the pathology of OA, RA, and bone malignancies, where dysregulated 14-3-3-mediated signaling cascades have been implicated in the disease processes. This review illuminates how the perturbation of 14-3-3 protein interactions can lead to the pathological manifestations observed in these disorders, including joint destruction and osteolytic activity. We highlight cutting-edge research that positions 14-3-3 proteins as potential biomarkers for disease progression and as innovative therapeutic targets, offering new avenues for disease intervention and management.

References

Kim K, Hsu A, Goo Lee H, Patel N, Chandhanayingyong C, Hickernell T . Proteomic identification of 14-3-3ϵ as a linker protein between pERK1/2 inhibition and BIM upregulation in human osteosarcoma cells. J Orthop Res. 2014; 32(6):848-54. DOI: 10.1002/jor.22598. View

Ngo S, Barry J, Nisbet J, Prins J, Whitehead J . Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes. Mol Cell Endocrinol. 2008; 302(1):33-40. DOI: 10.1016/j.mce.2008.10.020. View

Fu W, Hettinghouse A, Chen Y, Hu W, Ding X, Chen M . 14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis. Ann Rheum Dis. 2021; 80(12):1615-1627. PMC: 8595573. DOI: 10.1136/annrheumdis-2021-220000. View

Johnell O, Kanis J . An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006; 17(12):1726-33. DOI: 10.1007/s00198-006-0172-4. View

Halskau Jr O, Ying M, Baumann A, Kleppe R, Rodriguez-Larrea D, Almas B . Three-way interaction between 14-3-3 proteins, the N-terminal region of tyrosine hydroxylase, and negatively charged membranes. J Biol Chem. 2009; 284(47):32758-69. PMC: 2781693. DOI: 10.1074/jbc.M109.027706. View

Chijimatsu R, Saito T . Mechanisms of synovial joint and articular cartilage development. Cell Mol Life Sci. 2019; 76(20):3939-3952. PMC: 11105481. DOI: 10.1007/s00018-019-03191-5. View

Gardino A, Yaffe M . 14-3-3 proteins as signaling integration points for cell cycle control and apoptosis. Semin Cell Dev Biol. 2011; 22(7):688-95. PMC: 3507455. DOI: 10.1016/j.semcdb.2011.09.008. View

An Y, Zhang H, Wang C, Jiao F, Xu H, Wang X . Activation of ROS/MAPKs/NF-κB/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis. FASEB J. 2019; 33(11):12515-12527. PMC: 6902677. DOI: 10.1096/fj.201802805RR. View

Sun Z, Ning Y, Wu H, Guo S, Jiao X, Ji J . 14-3-3ζ targets β-catenin nuclear translocation to maintain mitochondrial homeostasis and promote the balance between proliferation and apoptosis in cisplatin-induced acute kidney injury. Cell Signal. 2023; 111:110878. DOI: 10.1016/j.cellsig.2023.110878. View

10.

Arrendale A, Kim K, Choi J, Li W, Geahlen R, Borch R . Synthesis of a phosphoserine mimetic prodrug with potent 14-3-3 protein inhibitory activity. Chem Biol. 2012; 19(6):764-71. PMC: 3392204. DOI: 10.1016/j.chembiol.2012.05.011. View

11.

Zhao R, He H, Zhu Y, Wan J, Li Y, Gao S . MiR-204/14-3-3ζ axis regulates osteosarcoma cell proliferation through SATA3 pathway. Pharmazie. 2018; 72(10):593-598. DOI: 10.1692/ph.2017.7574. View

12.

Ji L, Wang Q, Liu M, Zhu C, Xiao Y, Han J . The 14-3-3 protein YWHAB inhibits glucagon-induced hepatic gluconeogenesis through interacting with the glucagon receptor and FOXO1. FEBS Lett. 2021; 595(9):1275-1288. DOI: 10.1002/1873-3468.14063. View

13.

Glyn-Jones S, Palmer A, Agricola R, Price A, Vincent T, Weinans H . Osteoarthritis. Lancet. 2015; 386(9991):376-87. DOI: 10.1016/S0140-6736(14)60802-3. View

14.

Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G, Bahar M . The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal. 2017; 15(1):23. PMC: 5480189. DOI: 10.1186/s12964-017-0177-y. View

15.

Tazawa H, Takahashi S, Zilliacus J . Interaction of the parathyroid hormone receptor with the 14-3-3 protein. Biochim Biophys Acta. 2003; 1620(1-3):32-8. DOI: 10.1016/s0304-4165(02)00503-2. View

16.

Dehlin M, Jacobsson L, Roddy E . Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat Rev Rheumatol. 2020; 16(7):380-390. DOI: 10.1038/s41584-020-0441-1. View

17.

Deng Z, Li Y, Gao X, Lei G, Huard J . Bone morphogenetic proteins for articular cartilage regeneration. Osteoarthritis Cartilage. 2018; 26(9):1153-1161. DOI: 10.1016/j.joca.2018.03.007. View

18.

Bier D, Rose R, Bravo-Rodriguez K, Bartel M, Ramirez-Anguita J, Dutt S . Molecular tweezers modulate 14-3-3 protein-protein interactions. Nat Chem. 2013; 5(3):234-9. DOI: 10.1038/nchem.1570. View

19.

Munier C, Ottmann C, Perry M . 14-3-3 modulation of the inflammatory response. Pharmacol Res. 2020; 163:105236. DOI: 10.1016/j.phrs.2020.105236. View

20.

Gelderblom H, Hogendoorn P, Dijkstra S, van Rijswijk C, Krol A, Taminiau A . The clinical approach towards chondrosarcoma. Oncologist. 2008; 13(3):320-9. DOI: 10.1634/theoncologist.2007-0237. View