Multiple roles of angiopoietin-like 4 in osteolytic disease

Journal article

Hypoxia and the Hypoxia-Inducible Factor (HIF) transcription factor drive pathological bone 2 loss in conditions including rheumatoid arthritis, osteoarthritis, osteoporosis, primary bone 3 tumours and bone metastatic cancer. There is therefore considerable interest in determining 4 the function(s) of HIF-induced genes in these pathologies. Angiopoietin-like 4 (ANGPTL4) 5 is an adipose-derived, HIF-1- and PPAR-induced gene that was originally discovered as an 6 endocrine and autocrine / paracrine regulator of lipid metabolism. Given the inverse 7 relationship between bone adiposity and fracture risk, ANGPTL4 might be considered a good 8 candidate for mediating the downstream effects of HIF-1 relevant to osteolytic disease. This 9 review will consider the possible roles of ANGPTL4 in regulation of osteoclast-mediated 10 bone resorption, cartilage degradation, angiogenesis and inflammation, focusing on results 11 obtained in the study of rheumatoid arthritis. Possible roles in other musculoskeletal 12 pathologies will also be discussed. This will highlight ANGPTL4 as a regulator of multiple 13 disease processes which could represent a novel therapeutic target in osteolytic 14 musculoskeletal disease.

Authors: Knowles, H

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Frontiers Media
• Journal: Frontiers in Endocrinology
• Volume: 8
• Pages: 80
• Publication date: 2017-04-01
• Acceptance date: 2017-03-30
• DOI: 10.3389/fendo.2017.00080
• EISSN: 1664-2392
• Keywords: angiogenesis; rheumatoid arthritis; Angiopoietin-like 4 (ANGPTL4); inflammation; bone resorption; cartilage degradation