The multifaced role of HtrA1 in the development of joint and skeletal disorders

Giovanni Tossetta; Sonia Fantone; Caterina Licini; Daniela Marzioni; Monica Mattioli-Belmonte

doi:10.1016/j.bone.2022.116350

The multifaced role of HtrA1 in the development of joint and skeletal disorders

Bone. 2022 Apr:157:116350. doi: 10.1016/j.bone.2022.116350. Epub 2022 Feb 5.

Authors

Giovanni Tossetta¹, Sonia Fantone², Caterina Licini³, Daniela Marzioni², Monica Mattioli-Belmonte³

Affiliations

¹ Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy; Clinic of Obstetrics and Gynaecology, Department of Clinical Sciences, Università Politecnica delle Marche, Salesi Hospital, Azienda Ospedaliero Universitaria, Ancona, Italy. Electronic address: g.tossetta@univpm.it.
² Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy.
³ Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Via Tronto 10/a, Ancona 60126, Italy.

PMID: 35131488
DOI: 10.1016/j.bone.2022.116350

Abstract

HtrA1 (High temperature requirement A1) family proteins include four members, widely conserved from prokaryotes to eukaryotes, named HtrA1, HtrA2, HtrA3 and HtrA4. HtrA1 is a serine protease involved in a variety of biological functions regulating many signaling pathways degrading specific components and playing key roles in many human diseases such as neurodegenerative disorders, pregnancy complications and cancer. Due to its role in the breakdown of many ExtraCellular Matrix (ECM) components of articular cartilage such as fibronectin, decorin and aggrecan, HtrA1 encouraged many researches on studying its role in several skeletal diseases (SDs). These studies were further inspired by the fact that HtrA1 is able to regulate the signaling of one of the most important cytokines involved in SDs, the TGFβ-1. This review aims to summarize the data currently available on the role of HtrA1 in skeletal diseases such as Osteoporosis, Rheumatoid Arthritis, Osteoarthritis and Intervertebral Disc Degeneration (IDD). The use of HtrA1 as a marker of frailty in geriatric medicine would represent a powerful tool for identifying older individuals at risk of developing skeletal disorders, evaluating an appropriate intervention to improve quality care in these people avoiding or improving age-related SDs in the elderly population.

Keywords: HtrA1; Intervertebral disc degeneration; Musculoskeletal disorders; Osteoarthritis; Osteoporosis; Rheumatoid arthritis.

Publication types

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

MeSH terms

Aged
Cartilage, Articular* / metabolism
High-Temperature Requirement A Serine Peptidase 1* / genetics
High-Temperature Requirement A Serine Peptidase 1* / metabolism
Humans
Intervertebral Disc Degeneration*
Musculoskeletal Diseases* / metabolism

Substances

High-Temperature Requirement A Serine Peptidase 1
HTRA1 protein, human