Orthodontic treatment for dentofacial deformity is fundamental throughout the entire management process of cleft lip and palate. Orthodontist is one of those who are indispensable in the comprehensive multidisciplinary cleft team. Cleft lip and palate patients have unique dentofacial characteristics which makes the treatment goals and strategies different from those of other patients in different stages. For newborns with cleft lip and palate, the main treatment includes presurgical orthopedics. For patients in their primary dentition stage, the treatment mainly focuses on the prevention of bad oral habits and severe malocclusion. For those in their mixed dentition stage, the treatment mainly consists of dentition preparation for alveolar bone grafting and skeletal growth modification. For patients in their permanent dentition stage, treatment strategies include orthodontic camaflouge treatment, combined orthodontic-orthognathic approach and segmental alveolar distraction osteogenesis. In addition to routine orthodontic treatment, orthodontists should pay special attention to managing the compliance of cleft lip and palate patients with unique psychological characteristics. By summarizing the state-of-art cleft lip and palate orthodontic care in the multidisciplinary team, this review aims to involve more orthodontic clinicians to join in the modern biopsychosocial medical practice of cleft lip and palate team approach and to improve the standard of care for cleft lip and palate patients.

Graphene family nanomaterials (GFNs) are highly popular in the field of bone tissue engineering because of their excellent mechanical properties, biocompatibility, and ability to promote the osteogenic differentiation of stem cells. GFNs play a multifaceted role in promoting the bone regeneration microenvironment. First, GFNs activate the adhesion kinase/extracellularly regulated protein kinase (FAK/ERK) signaling pathway through their own micromorphology and promote the expression of osteogenesis-related genes. Second, GFNs adapt to the mechanical strength of bone tissue, which helps to maintain osseointegration; by adjusting the stiffness of the extracellular matrix, they transmit the mechanical signals of the matrix to the intracellular space with the help of focal adhesions (FAs), thus creating a favorable physiochemical microenvironment. Moreover, they regulate the immune microenvironment at the site of bone defects, thus directing the polarization of macrophages to the M2 type and influencing the secretion of relevant cytokines. GFNs also act as slow-release carriers of bioactive molecules with both angiogenic and antibacterial abilities, thus accelerating the repair process of bone defects. Multiple types of GFNs regulate the bone regeneration microenvironment, including scaffold materials, hydrogels, biofilms, and implantable coatings. Although GFNs have attracted much attention in the field of bone tissue engineering, their application in bone tissue regeneration is still in the basic experimental stage. To promote the clinical application of GFNs, there is a need to provide more sufficient evidence of their biocompatibility, elucidate the mechanism by which they induce the osteogenic differentiation of stem cells, and develop more effective form of applications.

Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.

Human adipose-derived stem cells (hASCs) are a promising cell type for bone tissue regeneration. Circular RNAs (circRNAs) have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis. However, how circRNAs regulate hASCs in osteogenesis is still unclear. Herein, we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs. Knockdown of circ_0003204 by siRNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs. We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p. We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 mRNA. The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis. Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model, while overexpression of circ_0003204 inhibited bone defect repair. Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.