Possible involvement of HtrA1 serine protease in the onset of osteoporotic bone extracellular matrix changes

被引:2
|
作者
Licini, C. [1 ]
Fantone, S. [2 ]
Lamanna, D. [1 ]
Tossetta, G. [3 ]
Marzioni, D. [3 ]
Belmonte, M. Mattioli [1 ]
机构
[1] Univ Politecn Marche, Dept Clin & Mol Sci DISCLIMO, Via Tronto 10-A, I-60126 Ancona, Italy
[2] IRCCS INRCA, Sci Direct, I-60124 Ancona, Italy
[3] Univ Politecn Marche, Dept Expt & Clin Med, Via Tronto 10-A, I-60126 Ancona, Italy
来源
TISSUE & CELL | 2024年 / 87卷
关键词
HtrA1; Osteoporosis; ECM; Bone Remodeling; Bone Formation; DIFFERENTIATION; OSTEOBLAST; CELLS;
D O I
10.1016/j.tice.2024.102329
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
High-temperature requirement A1 (HtrA1), a multidomain serine protease acting on Extracellular matrix (ECM) rearrangement, is also secreted by osteoblasts and osteoclasts. Recent and conflicting literature highlights HtrA1's role as a controller of bone remodeling, proposing it as a possible target for pathologies with unbalanced bone resorption, like Osteoporosis (OP). To add knowledge on this molecule function in bone physiopathology, here we compared HtrA1 distribution in the ECM of healthy (H) and OP bone tissue, also examining its localization in the sites of new bone formation. HtrA1 was homogeneously expressed in the mature bone ECM of H tissue showing a 55.6 +/- 16.4% of the stained area, with a significant (p=0.0001) decrease in OP percentage stained area (21.1 +/- 13.1). Moreover, HtrA1 was present in the endosteum and cells involved in osteogenesis, mainly in those "entrapped" in woven bone, whereas osteocytes in mature lamellar bone were negative. Based on our previous observation in OP tissue of a significantly increased expression of Decorin and Osteocalcin, both involved in bone mineralization and remodeling and equally substrates for HtrA1, we speculate that HtrA1 by controlling the proper amount of Decorin and Osteocalcin favors normal bone maturation and mineralization. Besides, we suggest that late-osteoblasts and pre-osteocytes secrete HtrA1 in the adjacent matrix whilst proceeding with their maturation and that HtrA1 expression is further modified during the remodeling from woven to the lamellar bone. Overall, our data suggest HtrA1 as a positive regulator of bone matrix formation and maturation: its reduced expression in mature OP bone, affecting protein content and distribution, could hamper correct bone remodeling and mineralization.
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页数:6
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