Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats |
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| Institution: | 1. Department of Rehabilitation, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province 110001, PR China;2. Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA;3. Department of Orthopedic Surgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang Province 163316, PR China;1. Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi''an 710032, People''s Republic of China;2. Air Force General Hospital, People''s Liberation Army, Beijing 100142, People''s Republic of China;1. Department of Organismal Animal Physiology, Institute for Water and Wetland Research, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands;2. Hubrecht Institute-KNAW & UMC Utrecht, Utrecht 3584 CT, The Netherlands;3. Institute for Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, WWU Münster, 48149 Münster, Germany;4. Cells-in-Motion Cluster of Excellence (EXC 1003 – CiM), University of Münster, Germany;1. Internal Medicine, Hospital of Piombino, Livorno, Italy;2. FADOI Foundation, Research Department, Milan, Italy;3. Department of Locomotor System, Division of Rheumatology, ASL3-Azienda Sanitaria Genovese, Genoa, Italy;4. Section of Osteoporosis and Musculoskeletal Diseases, Department of Radiological, Oncological and Anatomical–Pathological Sciences, University “La Sapienza”, Rome, Italy;5. Rheumatology, “G. Pini” Institute, Milan, Italy;6. Department of Medical, Surgical and Neurological Sciences, University of Siena, Italy;7. Internal Medicine, Hospital of Ceva, Cuneo, Italy;8. Internal Medicine, Hospital Pugliese-Ciaccio, Catanzaro, Italy;9. Internal Medicine, Azienda Ospedaliero-Universitaria “S. Anna”, Ferrara, Italy;10. QBGroup SpA, Padova, Italy;11. Department of Internal Medicine I, Arcispedale S. Maria Nuova, Reggio Emilia, Italy;12. Medical Department, “Civile” Hospital, Legnano, Italy;13. Department of Internal Medicine, Hospital “Maggiore della Carità”, Novara, Italy;1. Department of Endocrinology, Royal North Shore Hospital, St Leonards, Australia;2. University of Sydney, Australia;3. NSW Cancer Council, Sydney, Australia;4. Department of Endocrine Surgery, Royal North Shore Hospital, St Leonards, Australia;1. Department of Orthodontics, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan;2. Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan |
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| Abstract: | Osteoarthritis (OA) is a most commonly multifactorial degenerative joint disease along with the aging population, particularly in postmenopausal women. During the onset of OA, articular cartilage and subchondral bone act in concert as a functional unit. This present study is to investigate the effects of early or late treatment with recombinant lubricin on the onset of osteoarthritis (OA) in ovariectomized (OVX) rats. We found that both early and late recombinant lubricin treatments attenuated the onset of OA by positive feedback loop between articular cartilage and subchondral bone, although late treatment contributed to a lesser effect compared with early treatment. Specifically, treatment with recombinant lubricin protected articular cartilage from degeneration, demonstrated by lower proteoglycan loss, lower OARSI scores, less calcification cartilage zone and reduced immunostaining for collagen X (Col X) and matrix metalloproteinase (MMP-13) but increased the expression of lubricin, in comparison with vehicle-treated OVX rat group. Further, chondroprotective effects of lubricin normalized bone remodeling in subchondral bone underneath. It's suggested that treatment with recombinant lubricin inhibited the elevation of TRAP and Osterix positive cells in OVX rats and led to the normalization of subchondral bone microarchitectures with the suppression of subsidence of bone volume ratio (BV/TV) and trabecular thickness (Tb.Th) and the increase of trabecular separation (Tb.Sp) in vehicle-treated OVX rats. What's more, the normalization of subchondral bone in turn attenuated the articular cartilage erosion by inhibiting vascular invasion from subchondral bone to calcified cartilage zone, exemplified by inhibiting the elevation of CD31 positive cells in calcified cartilage and angiography in subchondral bone. Together, these results shed light that both early and late recombinant lubricin treatments attenuate the onset of OA by balancing the interplay between articular cartilage and subchondral bone in OVX rats, while also providing a further rationale for its therapeutic targeting to postmenopausal OA and suggesting that treatment timing is a pivotal factor for better effect acquisition. |
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