Human high‐temperature requirement protein 1 (HTRA1) is a member of serine proteases and consists of four well‐defined domains—an IGFBP domain, a Kazal domain, a protease domain and a PDZ domain. HTRA1 is a secretory protein and also present intracellularly and associated with microtubules. HTRA1 regulates a broad range of physiological processes via its proteolytic activity. This review examines the role of HTRA1 in bone biology, osteoarthritis, intervertebral disc (IVD) degeneration and tumorigenesis. HTRA1 mediates diverse pathological processes via a variety of signalling pathways, such as TGF‐β and NF‐κB. The expression of HTRA1 is increased in arthritis and IVD degeneration, suggesting that HTRA1 protein is attributed to cartilage degeneration and disease progression. Emerging evidence also suggests that HTRA1 has a role in tumorigenesis. Further understanding the mechanisms by which HTRA1 displays as an extrinsic and intrinsic regulator in a cell type–specific manner will be important for the development of HTRA1 as a therapeutic target.

中文翻译：

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分子结构和高温需求蛋白 1 在骨骼疾病和癌症中的作用

人类高温需求蛋白 1 (HTRA1) 是丝氨酸蛋白酶的成员，由四个明确定义的结构域组成——IGFBP 结构域、Kazal 结构域、蛋白酶结构域和 PDZ 结构域。HTRA1 是一种分泌蛋白，也存在于细胞内并与微管相关。HTRA1 通过其蛋白水解活性调节范围广泛的生理过程。本综述研究了 HTRA1 在骨生物学、骨关节炎、椎间盘 (IVD) 变性和肿瘤发生中的作用。HTRA1 通过多种信号通路介导多种病理过程，如 TGF-β 和 NF-κB。HTRA1 的表达在关节炎和 IVD 变性中增加，表明 HTRA1 蛋白归因于软骨变性和疾病进展。新出现的证据还表明 HTRA1 在肿瘤发生中起作用。