Abstract
As a consequence of the avascular nature of cartilage the microenvironment in which chondrocytes must exist is characterized by hostile conditions, most prominently very low levels of oxygen (hypoxia). In recent years, a vast number of papers reporting on the role of hypoxia in cartilage development and disease has been published. It is well established today that the principal mediator of cellular adaptation to hypoxia, the transcription factor hypoxia inducible factor (HIF)-1, is of pivotal importance for survival and growth arrest of chondrocytes during cartilage development as well as energy generation and matrix synthesis of chondrocytes in healthy as well as osteoarthritic cartilage. With this commentary we aim to briefly discuss the recently published literature in this field.
Highlights
hypoxia inducible factor (HIF)-1, as the key molecule in the adaptive response of cells and tissues to low oxygen levels, is responsible for increased expression of erythropoietin, glucose transporters, glycolytic enzymes, pro-angiogenic factors and several other molecules involved in apotosis and cell proliferation [5]
Several groups have demonstrated that HIF-1 is of pivotal importance in a diverse set of physiological and pathological conditions such as tumorigenesis, inflammation, cell survival in ischemic tissues and development of the growth plate as well as other organ systems [6,7]
It has been shown that HIF-1α accumulates and translocates into the nucleus after exposing chondrocytes to low oxygen levels and inflammatory cytokines [11,12,13]
Summary
The results provided in the study by Yudoh and colleagues and previous reports by us and other groups strongly support the notion that HIF-1 is of pivotal importance in cartilage development and homeostasis. Given the decreased oxygen levels and presence of inflammatory mediators during the course of OA, a causal role for HIF-1 in preventing cartilage damage is reasonable to assume. It seems likely that OA chondrocytes, which are metabolically activated, rely on HIF-1 to instigate anaerobic ATP generation via increased glucose uptake and utilization in order to compensate for the accelerated energy consumption during OA. The study by Yudoh and colleagues, in concert with previous reports, further characterized HIF-1 as a central factor for chondrocyte survival amidst the hostile microenvironmental conditions of OA, most prominently hypoxia, low pH, high lactic acid concentration and exposure to inflammatory cytokines
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
