Natural Products as Sources of Novel Drug Candidates for the Pharmacological Management of Osteoarthritis: A Narrative Review

Osteoarthritis is a chronic degenerative articular disorder. Formation of bone spurs, synovial inflammation, loss of cartilage, and underlying bone restructuring have been reported to be the main pathologic characteristics of osteoarthritis symptoms. The onset and progression of osteoarthritis are attributed to various inflammatory cytokines in joint tissues and fluids that are produced by chondrocytes and/or interact with chondrocytes, as well as to low-grade inflammation in intra-articular tissues. Disruption of the equilibrium between the synthesis and degradation of the cartilage of the joint is the major cause of osteoarthritis. Hence, developing a promising pharmacological tool to restore the equilibrium between the synthesis and degradation of osteoarthritic joint cartilage can be a useful strategy for effectively managing osteoarthritis. In this review, we provide an overview of the research results pertaining to the search for a novel candidate agent for osteoarthritis management via restoration of the equilibrium between cartilage synthesis and degradation. We especially focused on investigations of medicinal plants and natural products derived from them to shed light on the potential pharmacotherapy of osteoarthritis.

Three-Dimensional Spheroid Formation of Cryopreserved Human Dental Follicle-Derived Stem Cells Enhances Pluripotency and Osteogenic Induction Properties

BACKGROUND: Enhancement and maintenance of the stemness of mesenchymal stem cells (MSCs) is one of the most important factors contributing to the successful in vivo therapeutic application of these cells. In this regard, three-dimensional (3D) spheroid formation has been developed as reliable method for increasing the pluripotency of MSCs. Moreover, using a new protocol, we have previously shown that dental tissues of extracted wisdom teeth can be effectively cryopreserved for subsequent use as a source of autologous stem cells. The main purpose of this study is to analyze the stemness and in vitro osteogenic differentiation potential of 3D spheroid dental MSCs compared with conventional monolayer cultured MSCs. METHODS: In this study, MSC-characterized stem cells were isolated and cultured from long-term cryopreserved dental follicles (hDFSCs), and then 2D hDFSCs were cultured under 3D spheroid-forming conditions using a newly designed microchip dish. The spheroids (3D hDFSCs) thus produced were investigated and characterized with respect to stemness, MSC marker expression, apoptosis, cell cycle analysis, extracellular matrix (ECM) production, and osteogenic and adipogenic differentiation properties. RESULTS: In terms of MSC and senescence markers, spheroid cells showed no difference when compared with 2D hDFSCs; however, 3D hDFSCs were observed to have a higher proportion of cell cycle arrest and a larger number of apoptotic cells. Moreover, spheroids showed substantially increased levels of pluripotency marker (early transcription factors) and ECM protein expression. Compared with 2D hDFSCs, there was also a notable enhancement in the osteogenic induction potential of spheroids, although no differences were observed with respect to in vitro adipogenesis. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate the application of a spheroid culture system for dental follicle-derived stem cells using a microchip dish. Although further studies are needed, including in vivo transplantation, the results obtained in this study indicate that spheroid hDFSCs derived from cryopreserved dental follicle tissues could be used as a valuable source of autologous stem cells for bone tissue regeneration.

Tumor resection from retromolar trigone, posterolateral maxilla, and anterior mandibular ramus using lower cheek flap approach: a case report and review of literature

A surgical approach involving the retromolar trigone, posterolateral maxilla, and pterygoid region is the most challenging in the field of maxillofacial surgery. The upper cheek flap (Weber-Ferguson incision) with subciliary extension and the maxillary swing approach have been considered as alternatives; however, neither approach provides sufficient exposure of the pterygoid region and the anterior portion of the mandibular ramus. In this report, we describe two cases in which a lower cheek flap approach was used for complete tumor resection in the retromolar trigone and the anterior mandibular ramus. This approach allows full exposure of the posterolateral maxilla and the pterygoid region as well as the retromolar trigone without causing major sensory disturbances to the lower lip. A mental nerve anastomosis after tumor resection was performed in one patient and resulted in approximately 90% sensory recovery in the lower lip. The lower cheek flap approach provides adequate exposure of the posterolateral maxilla, including the pterygoid, retromolar trigone, and mandibular ramus areas. If the mental nerve can be anastomosed during flap approximation, postoperative sensory disturbances to the lower lip can be minimized.

Stability of unilateral sagittal split ramus osteotomy for correction of facial asymmetry: long-term case series and literature review

Bilateral sagittal split ramus osteotomy is considered a standard technique in mandibular orthognathic surgeries to reduce unexpected bilateral stress in the temporomandibular joints. Unilateral sagittal split ramus osteotomy (USSO) was recently introduced to correct facial asymmetry caused by asymmetric mandibular prognathism and has shown favorable outcomes. If unilateral surgery could guarantee long-term postoperative stability as well as favorable results, operation time and the incidence of postoperative complications could be reduced compared to those in bilateral surgery. This report highlights three consecutive cases with long-term follow-up in which USSO was used to correct asymmetric mandibular prognathism. Long-term postoperative changes in the condylar contour and ramus and condylar head length were analyzed using routine radiography and computed tomography. In addition, prior USSO studies were reviewed to outline clear criteria for applying this technique. In conclusion, patients showing functional-type asymmetry with predicted unilateral mandibular movement of less than 7 mm can be considered suitable candidates for USSO-based correction of asymmetric mandibular prognathism with or without maxillary arch surgeries.

Assessment of functional improvement with temporalis myofascial flap after condylectomy in elderly patients with anterior disc displacement without reduction and an erosive condylar surface / 대한악안면성형재건외과학회지

BACKGROUND: The purpose of this study was to investigate the functional effects of temporalis myofascial flap after condylectomy, with or without disc removal, in elderly patients with anterior disc displacement (ADD) without reduction and an erosive condylar surface of the temporomandibular joint (TMJ). METHODS: A total of 15 joints from 11 elderly patients (71-78 years old) were included. The patients had pain, mandibular dysfunction symptoms, and unilateral or bilateral ADD as well as an erosive condylar surface of the TMJ. All patients underwent temporalis myofascial flap reconstruction after condylectomy, with or without disc removal. If the maximal mouth opening (MMO) remained <35 mm after condylectomy, coronoidotomy was also performed. Self-assessed pain and mandibular function, including MMO and protrusive and lateral movements, were evaluated. RESULTS: No patient experienced serious complications. Most measurements improved significantly after surgery compared to preoperatively. Most patients achieved nearly-normal mouth opening at 4 weeks after surgery. Although most patients felt discomfort during active postoperative physiotherapy, no patient reported serious pain during the follow-up period. CONCLUSION: Although nonsurgical therapy is often the first treatment choice for ADD without reduction of the TMJ, surgical intervention involving condylectomy and temporalis myofascial flap reconstruction may be a reasonable first option for elderly patients with an erosive condylar surface of the TMJ.

Successful Localization of Intraoral Foreign Body with C-arm Fluoroscopy / 대한악안면성형재건외과학회지

During surgical procedures, unexpected material, including surgical instruments and tissue segments, may get lost in the surgical field. Most of these should be immediately removed to prevent further complications, such as vital organ irritation, infection, and inflammatory pseudo-tumor formation. However, it is not always easy to define the exact location of the foreign body, especially if the item is very small and/or it is embedded in the soft tissue of the head and neck region. Intraoperative real-time radiological imaging with C-arm fluoroscopy can be useful to trace the three-dimensional location of small and embedded foreign bodies in the oral and maxillofacial area. We describe an unusual case of an embedded micro-screw in the intrinsic tongue muscle that had been dropped into the sublingual space during a lower alveolar bone graft procedure. The lost foreign body was accurately identified with C-arm fluoroscopy and safely removed without any further complications.

Angiokeratoma circumscriptum of the buccal mucosa: a case report and literature review

Angiokeratoma is a benign cutaneous lesion of the capillaries, presenting as dilated vessels in the upper part of the dermis. Although this disorder is classified into various types and has been occasionally reported in the skin of the scrotum or extremities, the involvement of the oral cavity mucosa has been rarely reported. The present study reports a case of angiokeratoma circumscriptum in the buccal mucosa. The expression of vascular endothelial growth factor (VEGF) and both of its receptors (VEGFR-1 and VEGFR-2) was demonstrated by immunohistochemistry in the endothelial cells lining the dilated vessels. The expression of VEGFR-2 was higher than that of VEGFR-1 in the endothelial cells in the lesion, indicating an increased rate of endothelial cell proliferation within the lesion. Interestingly, some of the endothelial cells co-expressed VEGF and its two receptors. These results suggest that endothelial cells in the pathologically dilated vessels possess VEGF autocrine growth activity involved in vasculogenesis and maintenance in angiokeratoma lesions. To our knowledge, this is the second report published on isolated oral angiokeratoma confined to the buccal mucosa and the first case report on angiokeratoma circumscriptum involving the buccal mucosa.

Slimming of Lower Face by Contouring of the Mandibular Body in Orthognathic Surgery Patients

Expansile keratocystic odontogenic tumor in the maxilla: immunohistochemical studies and review of literature

Keratocystic odontogenic tumors (KCOT) - previously termed odontogenic keratocysts (OKC) - are characterized by aggressive behavior and a high rate of recurrence. Histopathologically, the basal layer of KCOT shows a higher cell proliferation rate and increased expression of anti-apoptosis genes. Clinically, KCOT is frequently involved in the mandibular posterior region but is not common in the posterior maxilla. However, it should be noted that due to its expansive characteristics, KCOT involved near the maxillary sinus could easily expand to an enormous size and occupy the entire maxilla. To achieve total excision of these expanded cystic tumors in the maxilla, a more aggressive approach would be needed. In this report, we describe two cases of expansile KCOT involving the entire unilateral maxilla and maxillary sinus; they were completely excised using the Weber-Ferguson approach, showing no evidence of recurrence during the follow-up period of more than two years. In immunohistochemical analyses of the tumor specimens, p53 and p63 showed strong expression, and B-cell lymphoma 2 (BCL2) and MKI67 (Ki-67) showed moderate or weak expression, however, detection of BCL2-associated X protein (BAX) was almost negative. These data indicate that expansile KCOT possesses increased anti-apoptotic activity and cell proliferation rate but decreased apoptosis. These properties of KCOT may contribute to tumor enlargement, aggressive behavior, and high recurrence rate.

OSTEOCHONDROMA OF THE MANDIBULAR CONDYLE AND ACCOMPANYING FACIAL ASYMMETRY: REPORT OF A CASE

Biomechanical Study of Rigidity in the External Fixators / 대한정형외과학회잡지

The finite element method was utilized to find the rigidity of the device in changing the parameters, such as geometrical configuration, material property, and loading condition in an external fixation. In the experimental analysis, a universal testing machine(UTM) was used to evaluate the rigidity of EBI, Monofixator and Hoffmann under the different type of lodings, such as axial compression, bending and torsion in changing the parameters. The result was compared with those of the experimental work. The results were as follows: 1) In standard condition, the yielding loads in axial compression were 85Kg in the EBI, 55Kg in the Hoffmann, and 100Kg in the Monofixator, The rigidity figures were 2930N/cm in the EBI, 764N/cm in the Hoffmann, and 2391M/cm in the Monofixator. Z) The experimental method was adapted to figure out the effect of parametric change on the stiffness of 3 different external fixation apparatus(Monofixator,EBI, Hoffmann). A Monofixator with a parametric change of pin diameter from 6mm to 5mm indicated 40% reduction of stiffness in axial compression and 60% reduction of stiffness in torsion. Also, in the case of the change of pin group separation from 20cm to 15cm it showed 64% increase of stiffness in, AP bending. EBI with the increase of the distance between pin and aluminum bar to 8cm showed 32% decrement of stiffness in axial compression and 38% decrement of stiffness in AP bending. The stiffness of the Hoffmann device was remarkable according to the number of the pin used and the distance between the pin and the aluminum bar. 3) Concerning the difference between the experimental analysis and finite element method in a Monofixator, the results of the experimental analysis were 10% to 37% lower than those of the finite element method. The reason is thought to be caused by complete binding. The obtained data shed light on the future guide-lines and future alterations of the design factors in external fixation device. Approprate use of the obtained information is desirable for the optimal,treatment of the fractured long bone.

Axisymmetric Contact Stress analysis of an Artificial Hip Joint of the Conical Fitting Type / 대한정형외과학회잡지

The purpose of this study is to investigate the effect of the ball-cone contact interface variation on the ceramic ball stress which is the dominant factor of the design of the moldular artificial hip joint. A contact stress analysis problem is formulated using the optimization principle and finite element analysis technique on the ball-cone system of three dimensional axi-symmetrical model, Numerical procedure is employed to get the solution for varying angles of cones and angular mismatches between the ball and cone interfaces. There is a fair amount of friction in the interface and included in the analysis model.