Highlights d Proteomic subgroups stratify patient survival and allocate specific treatments d Alterations of the liver-specific proteome and metabolism in HCC are identified d Multi-omics profile of key signaling and metabolic pathways in HCC is depicted d CTNNB1 mutation-associated ALDOA phosphorylation promotes HCC cell proliferation

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Osteoarthritis is a common disease that can cause severe pain and dysfunction in any joint, including the temporomandibular joint (TMJ). TMJ osteoarthritis (TMJOA) is an important subtype in the classification of temporomandibular disorders. TMJOA pathology is characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic inflammation in the synovial tissue. However, the exact pathogenesis and process of TMJOA remain to be understood. An increasing number of studies have recently focused on inflammation and remodeling of subchondral bone during the early stage of TMJOA, which may elucidate the possible mechanism of initiation and progression of TMJOA. The treatment strategy for TMJOA aims at relieving pain, preventing the progression of cartilage and subchondral bone destruction, and restoring joint function. Conservative therapy with nonsteroidal anti-inflammatory drugs, splint, and physical therapy, such as low-energy laser and arthrocentesis, are the most common treatments for TMJOA. These therapies are effective in most cases in relieving the signs and symptoms, but their long-term therapeutic effect on the pathologic articular structure is unsatisfactory. A treatment that can reverse the damage of TMJOA remains unavailable to date. Treatments that prevent the progression of cartilage degradation and subchondral bone damage should be explored, and regeneration for the TMJ may provide the ideal long-term solution. This review summarizes the current understanding of mechanisms underlying the pathogenesis and treatment of TMJOA.

BackgroundOsteoarthritis (OA) is an important subtype of temporomandibular disorders. A simple and reproducible animal model that mimics the histopathologic changes, both in the cartilage and subchondral bone, and clinical symptoms of temporomandibular joint osteoarthritis (TMJOA) would help in our understanding of its process and underlying mechanism.ObjectiveTo explore whether injection of monosodium iodoacetate (MIA) into the upper compartment of rat TMJ could induce OA-like lesions.MethodsFemale rats were injected with varied doses of MIA into the upper compartment and observed for up to 12 weeks. Histologic, radiographic, behavioral, and molecular changes in the TMJ were evaluated by light and electron microscopy, MicroCT scanning, head withdrawal threshold test, real-time PCR, immunohistochemistry, and TUNEL assay.ResultsThe intermediate zone of the disc loosened by 1 day post-MIA injection and thinned thereafter. Injection of an MIA dose of 0.5 mg or higher induced typical OA-like lesions in the TMJ within 4 weeks. Condylar destruction presented in a time-dependent manner, including chondrocyte apoptosis in the early stages, subsequent cartilage matrix disorganization and subchondral bone erosion, fibrosis, subchondral bone sclerosis, and osteophyte formation in the late stages. Nociceptive responses increased in the early stages, corresponding to severe synovitis. Furthermore, chondrocyte apoptosis and an imbalance between anabolism and catabolism of cartilage and subchondral bone might account for the condylar destruction.ConclusionsMulti-level data demonstrated a reliable and convenient rat model of TMJOA could be induced by MIA injection into the upper compartment. The model might facilitate TMJOA related researches.

A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental.

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Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio.

The immune system plays a pivotal role during bone remodeling process. Orthodontic tooth movement (OTM) induces local inflammation in periodontium, but whether systemic immune response is involved in OTM remains unknown. In this study, we show that tooth movement distance was significantly reduced in T-cell-deficient immunocompromised mice compared with wild-type (WT) mice. Intravenous infusion of allogeneic T cells to the immunocompromised mice rescued the OTM distance. Correspondingly, increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts were detected around the alveolar bone after OTM in WT mice but were barely detected in immunocompromised mice. Moreover, intravenous infusion of T cells rescued the number of TRAP-positive osteoclasts in the OTM area of the immunocompromised mice, thus suggesting T cells are required for OTM. We then reveal that OTM induced a significant elevation of type 1 T helper cell (Th1) cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) around periodontal tissue in WT but not in immunocompromised mice. Infusion of T cells could increase the levels of TNF-α and IFN-γ in periodontal tissues of immunocompromised mice. More interestingly, intraperitoneal injection of TNF-α inhibitor etanercept significantly reduced the distance of OTM in T-cell-infused immunocompromised mice. In summary, this study demonstrates a previously unrecognized mechanism that T cells are required for OTM depending on Th1-associated cytokines.