LRP receptors in chondrocytes are modulated by simulated microgravity and cyclic hydrostatic pressure


Autoři: Rachel C. Nordberg aff001;  Liliana F. Mellor aff002;  Andrew R. Krause aff003;  Henry J. Donahue aff004;  Elizabeth G. Loboa aff001
Působiště autorů: College of Engineering, University of Missouri, Columbia, Missouri, United States of America aff001;  Spanish National Cancer Research Centre, Madrid, Spain aff002;  Sport Health and Physical Education, Vancouver Island University, Nanaimo, British Columbia, Canada aff003;  Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, Hershey, Pennsylvania, United States of America aff004;  Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223245

Souhrn

Mechanical loading is essential for the maintenance of musculoskeletal homeostasis. Cartilage has been demonstrated to be highly mechanoresponsive, but the mechanisms by which chondrocytes respond to mechanical stimuli are not clearly understood. The goal of the study was to determine how LRP4, LRP5, and LRP6 within canonical Wnt-signaling are regulated in simulated microgravity and cyclic hydrostatic pressure, and to investigate the potential role of LRP 4/5/6 in cartilage degeneration. Rat chondrosacroma cell (RCS) pellets were stimulated using either cyclic hydrostatic pressure (1Hz, 7.5 MPa, 4hr/day) or simulated microgravity in a rotating wall vessel (RWV) bioreactor (11RPM, 24hr/day). LRP4/5/6 mRNA expression was assessed by RT-qPCR and LRP5 protein expression was determined by fluorescent immunostaining. To further evaluate our in vitro findings in vivo, mice were subjected to hindlimb suspension for 14 days and the femoral heads stained for LRP5 expression. We found that, in vitro, LRP4/5/6 mRNA expression is modulated in a time-dependent manner by mechanical stimulation. Additionally, LRP5 protein expression is upregulated in response to both simulated microgravity and cyclic hydrostatic pressure. LRP5 is also upregulated in vivo in the articular cartilage of hindlimb suspended mice. This is the first study to examine how LRP4/5/6, critical receptors within musculoskeletal biology, respond to mechanical stimulation. Further elucidation of this mechanism could provide significant clinical benefit for the identification of pharmaceutical targets for the maintenance of cartilage health.

Klíčová slova:

Cartilage – Hydrostatic pressure – Chondrocytes – Mouse models – Osteoarthritis – Wnt signaling cascade – Artificial gravity – Articular cartilage


Zdroje

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