title: Acroosteolysis in systemic sclerosis: An insight into hypoxia-related pathogenesis.
abstract: Acro-osteolysis, or bony resorption of the terminal digital tufts, is a well-recognized, but under-researched, feature of systemic sclerosis. The mechanisms that disturbs local homeostatic balance of bone formation and resorption in favor of osteoclast activation and pathological bone loss remain to be established. Vascular alterations and reduced capillary density impair tissue oxygenation in systemic sclerosis, and the resulting hypoxia might contribute directly to the disease progression. In this paper we summarize the current evidence for hypoxia as the common pathophysiological denominator of digital vasculopathy and enhanced osteoclastic activity in systemic sclerosis-associated acroosteolysis. The hypoxia-inducible transcription factor HIF-1α and VEGF signaling has a critical role in regulating osteoclastic bone-resorption and angiogenesis, and increased osteoclastogenesis and higher VEGF levels may contribute to acroosteolysis in systemic sclerosis. The cells of the osteoblast lineage also have important roles in angiogenic-osteogenic coupling. The research in this field might help limiting the disability associated with the disease.
authors.affiliation: Rheumatology Department, 'Iuliu Hațieganu' University of Medicine and Pharmacy Cluj, 400012 Cluj-Napoca, Romania; Rheumatology Department, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania.
authors.forename: Simon
authors.initials: S
authors.lastname: Siao-Pin
authors.affiliation: Rheumatology Department, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania.
authors.forename: Laura-Otilia
authors.initials: LO
authors.lastname: Damian
authors.affiliation: Rheumatology Department, 'Iuliu Hațieganu' University of Medicine and Pharmacy Cluj, 400012 Cluj-Napoca, Romania; Rheumatology Department, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania.
authors.forename: Laura Mirela
authors.initials: LM
authors.lastname: Muntean
authors.affiliation: Rheumatology Department, 'Iuliu Hațieganu' University of Medicine and Pharmacy Cluj, 400012 Cluj-Napoca, Romania; Rheumatology Department, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Rednic
keywords: VEGF; acroosteolysis; angiogenesis; bone cells; hypoxia; systemic sclerosis