Pedunculated Osteochondroma Presenting as Verruca Vulgaris: A Diagnosis Requiring a High Index of Suspicion: Case Report.

Introduction: Osteochondromas are the most common benign tumors of the bone and can be sessile or pedunculated. Although osteochondromas are typically seen in the long bones, they are rarely seen in the small bones of the hand or foot. Verruca vulgaris, also known as the common wart, is one of the most common skin conditions presenting to physicians and must be distinguished either clinically or histologically from other hyperkeratotic conditions, including bone conditions such as bone tumors that can place pressure on the skin and cause callus formation that can mimic a wart or create skin deformity. A high index of suspicion for underlying bone mass or tumor should be entertained when evaluating patients for skin conditions, particularly of the hand or foot, with failure to improve with treatment. Case Report: This case report presents a 20-year-old male with a pedunculated osteochondroma of the left fourth distal phalanx with hyperkeratotic skin overlying the mass at the end of the toe. He was initially treated by a family doctor and podiatrist for verruca vulgaris for over 5 years with two treatments of liquid nitrogen cryotherapy and surgical excision of the mass when the treating podiatrist encountered bone and recommended radiographs. The family requested follow-up with our practice several days later after they were told the patient had a bone tumor. The patient requested surgical excision of the osteochondroma secondary to pain with activities and difficulties with his vocation as a pilot. Conclusion: All physicians must be mindful of an underlying bone tumor or mass in patients presenting with skin changes, particularly about the foot or hand. Knowledge that an underlying bone tumor can present as a verruca vulgaris may prevent a delay in diagnosis or unnecessary treatment when evaluating and treating a patient with a skin lesion. Fortunately, our case was a benign osteochondroma; a malignant tumor with a delay in diagnosis could lead to loss of limb or life.

Double Squeeze Reduction Clamp Technique for Fracture Stabilization: A Case Report.

Introduction: The double squeeze technique for fracture stabilization is a technique in which the surgeon uses a second reduction clamp to hold and stabilize a smaller reduction clamp that reduces a fracture or plate yet is too small to hold by itself. This technique greatly assists anatomic fracture reduction and stabilization and allows the surgeon to complete the operation when there is limited reduction instrumentation available, or the surgeon needs more excursion on a small clamp holding a fracture and does not want to change instruments and possibly lose a reduction. We present a case of the double squeeze clamp technique, which to our knowledge has not been reported, to facilitate limited open reduction percutaneous plate stabilization in a distal tibia fracture. Case Report: This case report presents an 18-year-old male with a closed, oblique, displaced right distal tibia fracture following a crush injury to the extremity with a tree while using a chainsaw. He was initially seen in the emergency room and was discharged home in a splint to follow-up with the orthopedic surgeon on call. The family requested follow-up with our practice 3 days later and requested surgery at their rural local hospital secondary to insurance reasons. Patient requested plate fixation to treat his fracture. Due to limited reduction instrumentation in the facility, a double squeeze reduction clamp technique using a pointed reduction clamp on a serrated reduction clamp that was too small to hold the plate on the reduced fracture accomplished stabilization of the plate on the fracture while screws were placed. Conclusion: The double squeeze reduction clamp technique using one reduction clamp on a smaller reduction clamp greatly increases the ability to successfully reduce and stabilize multiple variations of different fractures whether secondary to differences in sizes of the bones, different types of bones, or in our case limited fracture reduction tools available.

Compartment Syndrome of the Gluteal Region: A Rare Condition Requiring a High Index of Suspicion.

Introduction: Compartment syndrome, an exceptionally rare condition, is a surgical emergency that can quickly escalate to limb ischemia and necrosis without treatment. Most cases occur post-trauma, typically affecting the anterior compartment of the leg. Patients present with pain out of proportion to their physical examination findings and often have an early hallmark discovery of pain with passive extension. Compartment syndrome of the buttock requires an even higher index of suspicion, as the condition is even more uncommon, and the diagnosis is complicated by it being difficult to palpate the affected area and passively extend the leg when the patient is supine. Case Report: This case report presents an 83-year-old female with compartment syndrome of the left gluteal region, status post-fall 1 day earlier. She was admitted to the medical team for observation and failed to respond to narcotic pain medication. The physical examination revealed firm, tense, left gluteal compartments with buttock hematoma and surrounding muscle induration, significant pain, and extremity weakness in the sciatic nerve distribution. An emergent fasciotomy was performed to decompress the affected compartments. Conclusion: All physicians must be mindful of gluteal compartment syndrome in patients complaining of buttock pain, especially after pelvic trauma, who present with buttock swelling, tense gluteal compartments, and severe gluteal pain. A delay in diagnosis or treatment can lead to severe consequences, including disability, irreversible gluteal muscle damage, sciatic nerve dysfunction, kidney failure, or death.

PPARδ Agonist Promotes Type II Cartilage Formation in a Rabbit Osteochondral Defect Model.

Osteoarthritis (OA) is a chronic degenerative joint disease accompanied by an inflammatory milieu that results in painful joints. The pathogenesis of OA is multifactorial, with genetic predisposition, environmental factors, and traumatic injury resulting in the direct or indirect loss of cartilage. The articular cartilage can also be damaged by direct focal traumatic injury. Articular cartilage provides a smooth, deformable bearing surface with a low coefficient of friction, increased contact area, and reduced contact stress. Articular type II hyaline cartilage lines the synovial joints and, when injured, has a limited ability for repair, except for the most superficial layers via diffusion from the synovial fluid, secondary to no blood supply, a complex structure, and a low metabolic rate. Restoring the articular surface can relieve pain and restore function. Although many strategies have been developed to regenerate type II collagen based on the extent of the lesion, surgical treatments are still evolving. The peroxisome proliferator-activated receptor delta (PPARδ) agonist and collagen treatment of mesenchymal stem cells (MSCs) enhance the chondrogenic capacity in vitro. We present a novel technique for cartilage restoration in a rabbit cartilage osteochondral defect model using a PPARδ agonist (GW0742)-infused 3D collagen scaffold to induce type II cartilage from MSCs.

Synthesis and Evaluation of PPARδ Agonists That Promote Osteogenesis in a Human Mesenchymal Stem Cell Culture and in a Mouse Model of Human Osteoporosis.

We synthesized a directed library of compounds to explore the structure-activity relationships of peroxisome proliferator-activated receptor δ (PPARδ) activation relative to mesenchymal stem cell (MSC) osteogenesis. Our scaffold used para-substituted cinnamic acids as a polar headgroup, a heteroatom and heterocycle core connecting units, and substituted phenyl groups for the lipophilic tail. Compounds were screened for their ability to increase osteogenesis in MSCs, and the most promising were examined for subunit specificity using a quantitative PPAR transactivation assay. Six compounds were selected for in vivo studies in an ovariectomized mouse model of human postmenopausal osteoporosis. Four compounds improved bone density in vivo, with two (12d and 31a) having activity comparable to that of GW0742, a well-studied PPARδ-selective agonist. 31a (2-methyl-4-[N-methyl-N-[5-methylene-4-methyl-2-[4-(trifluoromethyl)phenyl]thiazole]]aminocinnamic acid) had the highest selectivity for PPARδ compared to other subtypes, its selectivity far exceeding that of GW0742. Our results confirm that PPARδ is a new drug target for possible treatment of osteoporosis via in situ manipulation of MSCs.

A natural supplement formula reduces anti-oxidative stress and enhances osteo-chondrogenic differentiation potential in mesenchymal stem cells.

There is great interest in using natural supplements to treat various medical conditions. In this study, we evaluated the anti-oxidative and stem cell differentiation effects of a mixture of vitamin D, Lactobacillus rhamnosus, ginger, curcumin, and Boswellia extract. The calcein acetoxymethyl assay after H2O2 treatment showed that combined natural supplement had an anti-oxidative effect. NS-J also increased calcium deposition, as shown by Alizarin Red S staining, indicating bone formation activity. The contents of type II collagen and glycosaminoglycans, which are biomarkers of cartilage, were higher in mesenchymal stem cells treated with combined natural supplement than in cells treated with individual ingredients of the formula. In mesenchymal stem cells treated with human osteoarthritis synovial fluids, combined natural supplement enhanced the expression of type II collagen and PPAR-δ, overcoming the anti-chondrogenic effect of inflammatory conditions. Combined natural supplement also inhibited Oil Red O staining in cells, which indicates inhibited adipogenesis. Thus, combined natural supplement, a formula comprising vitamin D, Lactobacillus rhamnosus, ginger, curcumin and Boswellia extract, reduced oxidative stress, enhanced osteogenesis and chondrogenesis, and inhibited adipogenesis in mesenchymal stem cells to a greater extent than the individual ingredients, indicating synergistic interaction. In addition, combined natural supplement increased the expression PPAR-δ, suggesting that these effects correlate with the PPAR-δ pathway.

PPAR-δ agonist affects adipo-chondrogenic differentiation of human mesenchymal stem cells through the expression of PPAR-γ.

INTRODUCTION: Peroxisome proliferator-activated receptor (PPAR) subfamily play an important role in chondrogenesis. Previous study has reported that mixture of GW0742 (PPAR-δ agonist), hyaluronic acid (HA) and mesenchymal stem cells (MSCs) enhance chondrogenesis. The purpose of this study is to compare with efficacies of commercially available HA and demonstrate correlation of PPAR-γ and PPAR-δ. METHODS: In this experimental study, MSCs were cultured with chondrogenic media and clinical HA gels (Euflexxa®, Synvisc®, Orthovisc® and Supartz®) using micormass culture method. Expression of type Ⅰ, Ⅱ collagen and matrix metalloprotease-13 (MMP-13) was measured by immunoblotting. MSCs were cultured with chondrogenic media and/or HA and/or GW0742 and/or rosiglitazone (PPAR-γ agonist) and/or human osteoarthritis synovial fluid. Immunoblotting was used to measure expression of type Ⅱ collagen and PPAR-γ. To identify the effective dose for chondrogenesis and adipogenesis, either 0.1, 1, 5 or 10 µM of rosiglitazone was added to MSCs in chondrogenic media or adipogenic media. RESULTS: Clinical HA gels inhibited expression of type Ⅰ collagen and enhanced the expression of MMP-13. Type Ⅱ collagen expression was significantly elevated in all treatment groups except Supartz®. GW0742 decreased the expression of PPAR-γ with/without inflammation condition. Rosiglitazone enhanced adipogenesis in a dose-dependent manner and enhanced the expression of type Ⅱ collagen under inflammation condition. Otherwise, the expression of type Ⅱ collagen and formation of chondrocyte spheroids showed a dose-dependent manner with a peak at 1 µM of rosiglitazone. CONCLUSIONS: PPAR-γ has a considerable anti-inflammatory effect and a strong pro-adipogenic effect, which inhibits the chondrogenic effect. PPAR-γ is related with PPAR-δ and shows a chondrogenic effect at lower concentrations. And clinical HA gels shows various efficacy of chondrogenesis. This study suggested that PPAR-γ and PPAR-δ are key regulatory factors of chondrogenesis.

PPAR-δ Agonist With Mesenchymal Stem Cells Induces Type II Collagen-Producing Chondrocytes in Human Arthritic Synovial Fluid.

Osteoarthritis (OA) is an inflammatory joint disease characterized by degeneration of articular cartilage within synovial joints. An estimated 27 million Americans suffer from OA, and the population is expected to reach 67 million in the United States by 2030. Thus, it is urgent to find an effective treatment for OA. Traditional OA treatments have no disease-modifying effect, while regenerative OA therapies such as autologous chondrocyte implantation show some promise. Nonetheless, current regenerative therapies do not overcome synovial inflammation that suppresses the differentiation of mesenchymal stem cells (MSCs) to chondrocytes and the expression of type II collagen, the major constituent of functional cartilage. We discovered a synergistic combination that overcame synovial inflammation to form type II collagen-producing chondrocytes. The combination consists of peroxisome proliferator-activated receptor (PPAR) δ agonist, human bone marrow (hBM)-derived MSCs, and hyaluronic acid (HA) gel. Interestingly, those individual components showed their own strong enhancing effects on chondrogenesis. GW0742, a PPAR-δ agonist, greatly enhanced MSC chondrogenesis and the expression of type II collagen and glycosaminoglycan (GAG) in hBM-MSC-derived chondrocytes. GW0742 also increased the expression of transforming growth factor ß that enhances chondrogenesis and suppresses cartilage fibrillation, ossification, and inflammation. HA gel also increased MSC chondrogenesis and GAG production. However, neither GW0742 nor HA gel could enhance the formation of type II collagen-producing chondrocytes from hBM-MSCs within human OA synovial fluid. Our data demonstrated that the combination of hBM-MSCs, PPAR-δ agonist, and HA gel significantly enhanced the formation of type II collagen-producing chondrocytes within OA synovial fluid from 3 different donors. In other words, the novel combination of PPAR-δ agonist, hBM-MSCs, and HA gel can overcome synovial inflammation to form type II collagen cartilage within human OA synovial fluid. This novel articularly injectable formula could improve OA treatment in the future clinical application.

Peroxisome proliferator-activated receptor delta agonist attenuates nicotine suppression effect on human mesenchymal stem cell-derived osteogenesis and involves increased expression of heme oxygenase-1.

Smoking has long been associated with osteoporosis, decreased bone mineral density, increased risk of bone fracture, and increased health costs. Nicotine, the main component of cigarette smoke, has major negative effects on bone metabolism and skeletal remodeling in vivo. Although osteoblasts and osteoblast-like cells have been used extensively to study the impact of nicotine, few studies have been performed on human mesenchymal stem cells (hMSCs). In this context, we examined the impact of nicotine on (a) hMSCs proliferation, (b) osteoblastic differentiation, (c) alkaline phosphatase (ALP) activity, and (d) expression of canonical genes during differentiation of hMSCs. MSCs isolated from human bone marrow were treated with different concentrations (0, 0.1, 1 and 10 µM) of nicotine for 7 days. Nicotine caused a dose-dependent decrease in cell proliferation, decreased heme oxygenase-1 (HO-1) expression (p < 0.05) and attenuated osteogenesis (p < 0.05) in hMSCs (45 % reduction at day 14). In addition, nicotine caused a dose-dependent decrease in alizarin red staining for calcium and staining for ALP. Induction of HO-1 by peroxisome proliferator-activated receptor delta agonist (GW0742) prevented the effect of nicotine. Nicotine caused a dose-dependent reduction in the expression of BMP-2, a well-known marker for bone formation; however, this was prevented by GW0742 treatment. Therefore, induction of HO-1 prevents the deleterious effects of nicotine on osteogenesis in hMSC. This offers insight into both how nicotine affects bone remodeling and a therapeutic approach to prevent fracture and osteoporosis in smokers.