N Ogasawara1, F Kano2, N Hashimoto3, H Mori4, Y Liu5, L Xia6, T Sakamaki7, H Hibi8, T Iwamoto9, E Tanaka10, A Yamamoto11. 1. Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan; Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan. Electronic address: c301651009@tokushima-u.ac.jp. 2. Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan. Electronic address: fkano@tokushima-u.ac.jp. 3. Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan. Electronic address: nhashimoto@tokushima-u.ac.jp. 4. Department of Pediatric Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan. Electronic address: h.mori@tokushima-u.ac.jp. 5. Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan; Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan. Electronic address: c301751019@tokushima-u.ac.jp. 6. Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan; Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan. Electronic address: c301951003@tokushima-u.ac.jp. 7. Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan. Electronic address: sakuma.takuma@tokushima-u.ac.jp. 8. Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. Electronic address: hibihi@med.nagoya-u.ac.jp. 9. Department of Pediatric Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan. Electronic address: iwamoto@tokushima-u.ac.jp. 10. Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan. Electronic address: etanaka@tokushima-u.ac.jp. 11. Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan. Electronic address: akihito@tokushima-u.ac.jp.
Abstract
OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. DESIGN: To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model. RESULTS: SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1β, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. CONCLUSIONS: Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA.
OBJECTIVE:Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. DESIGN: To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murineTMJOA model. RESULTS: SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1β, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. CONCLUSIONS: Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouseTMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA.