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Intravenous administration of conditioned medium from stem cells of human exfoliated deciduous teeth (SHED-CM) effectively restores mechanically injured osteochondral tissues in mouse temporomandibular joint osteoarthritis. However, the underlying therapeutic mechanisms remain elusive. Here, we investigated the direct therapeutic effects of SHED-CM on inflamed primary condylar chondrocytes in vitro. Immunofluorescence staining revealed that interleukin-1β-stimulated chondrocytes showed increased expression of the catabolic marker inducible nitric oxide synthase (iNOS) and reduced expression of the anabolic marker aggrecan (ACAN). We found that SHED-CM treatment, but not conditioned medium from bone marrow mesenchymal stem cells (BMSC-CM), effectively suppressed iNOS expression and elevated ACAN levels, indicating that SHED-CM converted the catabolic phenotype of inflamed chondrocytes to an anabolic phenotype. Liquid chromatography with tandem mass spectrometry analysis of SHED-CM and BMSC-CM identified eight proteins enriched in SHED-CM that are related to anti-inflammatory and/or chondrogenic processes. Of these proteins, the Wnt signal inhibitor secreted frizzled-related protein 1 (SFRP1) was the most abundantly enriched in SHED-CM. We found that treatment with the selective SFRP1 inhibitor WAY-316606 abolished the anti-catabolic and pro-anabolic effects of SHED-CM. Collectively, our study suggests that SHED-CM directly suppresses catabolism and promotes anabolic responses of inflamed primary condylar chondrocytes, which partially rely on SFRP1 function in SHED-CM. The direct action of SHED-CM may be useful to treat inflammatory cartilage diseases.

Inflammatory (M1-polarized) macrophages cause neuropathic pain (NP) after nerve injury through non-resolving neuroinflammation. However, increasing evidence suggests that converting M1 to anti-inflammatory M2 macrophages may rescue NP. In the present study, the therapeutic potential of low-intensity pulsed ultrasound (LIPUS) was investigated in a partial sciatic nerve ligation (PSL)-induced NP model. Materials and Methods: Abnormal pain sensation, such as tactile allodynia, was caused by PSL. Immediately after PSL induction, the mice were subjected to LIPUS treatment for 20 min/day for 7 days. LIPUS was used at an average intensity of 60 mW/cm2 and a frequency of 1.5 MHz. Results: In the behavioral test, the LIPUS group showed a significant improvement in the PSL-induced hypersensitivity compared to the PSL group not exposed to LIPUS. We found an increasing number of M2 macrophages in the injured sciatic nerves after LIPUS exposure. LIPUS treatment decreased expression of pro-inflammatory microglial markers in spinal cord. Conclusions: Our data suggest that LIPUS has an anti-nociceptive effect by increasing anti-inflammatory M2 macrophage and may be a suitable therapeutic candidate for NP.

Objective: We aimed to identify the immunoregulatory role of the cyclin-dependent kinase inhibitor p21 in the homeostasis of mandibular condylar cartilage affected by mechanical stress. Materials and Methods: Ten C57BL/6 wild-type (WT) and ten p21–/– mice aged 8 weeks were divided into the untreated and treated groups. In the treated groups, mechanical stress was applied to the temporomandibular joint (TMJ) through forced mouth opening for 3 h/day for 7 days. The dissected TMJs were assessed using micro-CT, histology, and immunohistochemistry. Results: Treated p21–/– condyles with mechanical stress revealed more severe subchondral bone destruction, with thinner cartilage layers and smaller proteoglycan area relative to treated WT condyles; untreated WT and p21–/– condyles had smoother surfaces. Immunohistochemistry revealed significant increases in the numbers of Caspase-3, interleukin-1β, matrix metalloprotease (MMP)-9, and MMP-13 positive cells, and few aggrecan positive cells, in treated p21–/– than in treated WT samples. Moreover, the number of TUNEL positive cells markedly increased in p21–/– condyles affected by mechanical stress. Conclusion: Our findings indicate that p21 in chondrocytes contributes to regulate matrix synthesis via the control of aggrecan and MMP-13 expression under mechanical stress. Thus, p21 might regulate the pathogenesis of osteoarthritis in the TMJ.

Radiation-induced skin ulceration is a frequent complication of radiotherapy for cancer treatment. Stem cells from human exfoliated deciduous teeth (SHEDs) can regenerate various tissues. In this study, we investigated the impact of SHED-conditioned media (SHED-CM) on radiation-induced ulceration. Mouse necks were locally irradiated with a single dose of 15 Gy of radiation. A week after the irradiation, most of the wild-type mice generated ulcer surrounded by severe erythema. Intra-venous administration of SHED-CM effectively inhibited the ulcer formation. Histological examination revealed that SHED-CM treatment inhibited radiation-induced dermal thickness and epithelial hyperplasia. SHED-CM could be a useful treatment option for radiation-induced skin ulceration.

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.

We report the case of a 40 year-old woman who presented third molar pericoronitis in neutropenia. she had undergone extraction of the right third mandibular molar. This may have been due to an infection in the extraction socket or part of the crown. There was no inflammation seen after transplant of umbilical cord blood. Keywords: Neutropenia, Pericoronitis, Oral infection