Elevated levels of 15-lipoxygenase-1 contribute to the abnormal phenotypes of osteoblasts in human osteoarthritis.

Abstract

AIMS:

15-lipoxygenase-1 (15-LOX-1) plays a vital role in aggravating the inflammatory response in various pathological processes, including osteoarthritis (OA). Abnormal osteoblast phenotypes including elevated runt-related transcription factor 2 (RUNX2), collagen type 1 alpha 1 (COL1), and osteocalcin (OCN) lead to osteosclerosis of the subchondral bone, which eventually causes OA. However, the pathogenesis of OA is poorly defined, and it is unclear if 15-LOX-1 induces osteoblast abnormal phenotypes in OA. Therefore, this study aimed to determine the roles of 15-LOX-1 on the abnormal phenotypes present in osteoblasts of the subchondral bone in OA.

MAIN METHODS:

The expression levels of 15-LOX-1 were measured by Immunohistochemistry, qRT-PCR and western blotting from the OA subchondral bone osteoblasts. To further investigate the roles of 15-LOX-1 in abnormal phenotypes of osteoblasts and its mechanisms in OA, 15-LOX-1 siRNA or overexpressing lv-15-lox-1 were transfected into osteoblasts, respectively. The effects of 15-LOX-1 on abnormal phenotypes of osteoblasts in OA were assessed by qRT-PCR, and western blotting. We also examined the role of 15-LOX-1-inhibited autophagy in OA osteoblasts by qRT-PCR, and western blotting, transmission electron microscopy.

KEY FINDINGS:

The expression levels of 15-LOX-1 along with osteoblast phenotype markers such as RUNX2, COL1, and OCN were significantly increased in OA subchondral bone. Furthermore, 15-LOX-1 inhibited autophagy significantly upregulated the expression levels of RUNX2, COL1 and OCN through activated mTORC1. Similarly, treatment with autophagy inhibitors alleviated osteoblast abnormal phenotypes of osteoblasts in OA.

SIGNIFICANCE:

In conclusion, our results suggested that the expression of 15-LOX-1 on osteoblasts from the subchondral bone increased in OA. 15-LOX-1 inhibited autophagy by activated mTORC1, which in turn upregulated the markers of abnormal osteoblast phenotypes RUNX2, COL1, and OCN.

• Authors: Yunpeng Wan, Dan Li, Yunxiang Lv, Minmin Wu, Lei Li, Zongsheng Yin
• Journal: Life sciences (Life Sci) Vol. 239 Pg. 116980 (Dec 15 2019) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 31704449 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• BGLAP protein, human
• Collagen Type I
• Collagen Type I, alpha 1 Chain
• Core Binding Factor Alpha 1 Subunit
• RUNX2 protein, human
• Osteocalcin
• Lipoxygenase
• Arachidonate 15-Lipoxygenase

Topics

• Arachidonate 15-Lipoxygenase (blood, metabolism)
• Bone and Bones (metabolism)
• Cells, Cultured
• Collagen Type I (metabolism)
• Collagen Type I, alpha 1 Chain
• Core Binding Factor Alpha 1 Subunit (metabolism)
• Humans
• Lipoxygenase (blood, metabolism)
• Osteoarthritis (metabolism)
• Osteoblasts (metabolism, pathology)
• Osteocalcin (metabolism)
• Phenotype