Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro Study.

Medical marijuana (versus Marijuana derivatives) has been reported to possess analgesic, immunomodulatory, and anti-inflammatory properties. Recent studies in animal models of arthritis showed that cannabinoids, a group of compounds produced from marijuana, may attenuate joint damage. However, whether marijuana byproducts can suppress osteoarthritis (OA)-associated cartilage degradation has not been previously reported. In this study, human chondrocytes were isolated from healthy articular cartilage, expanded in vitro, and subjected to pellet culture in a chondrogenic medium to form cartilage tissues. We first examined the influence of marijuana byproducts on normal cartilage by treating chondrocyte-derived tissues with a synthetic cannabinoid agonist, Win-55,212-2 (Win), at different concentrations ranging from 0.01 to 10 µM. After treatment, the tissue phenotype was assessed using glycosaminoglycan (GAG) assay and real-time PCR. Next, cartilage tissues were pre-treated with interleukin-1ß (IL-1ß) to generate an inflamed phenotype and then cultured with Win to assess its therapeutic potential. The results showed that at concentrations lower than 1 µM, Win treatment did not significantly impair chondrocyte growth or cartilage formation capacity, but at a high level (>10 µM), it remarkably suppressed cell proliferation. Interestingly, under the condition of IL-1ß pre-treatment, Win was able to partially preserve the cartilage matrix and decrease the production of interleukin-6, although the protective effect was mild. Taken together, our results indicated that the variable effects of Win on chondrocytes occur in a concentration-dependent manner. Whether cannabinoid derivatives can be used to treat cartilage degradation or can alter other structural changes in OA deserve further investigation.

Generation of hyaline-like cartilage tissue from human mesenchymal stromal cells within the self-generated extracellular matrix.

Chondrocytic hypertrophy, a phenotype not observed in healthy hyaline cartilage, is often concomitant with the chondrogenesis of human mesenchymal stromal cells (hMSCs). This undesired feature represents one of the major obstacles in applying hMSCs for hyaline cartilage repair. Previously, we developed a method to induce hMSC chondrogenesis within self-generated extracellular matrix (mECM), which formed a cartilage tissue with a lower hypertrophy level than conventional hMSC pellets. In this study, we aimed to test the utility of hypoxia and insulin-like growth factor-1 (IGF1) on further reducing hypertrophy. MSC-mECM constructs were first subjected to chondrogenic culture in normoxic or hypoxic (5%) conditions. The results indicated that hMSC-derived cartilage formed in hypoxic culture displayed a significantly reduced hypertrophy level than normoxic culture. However, hMSC chondrogenesis was also suppressed under hypoxic culture, partially due to the reduced activity of the IGF1 pathway. IGF1 was then supplemented in the chondrogenic medium, which promoted remarkable hMSC chondrogenesis under hypoxic culture. Interestingly, the IGF1-enhanced hMSC chondrogenesis, under hypoxic culture, was not at the expense of promoting significantly increased hypertrophy. Lastly, the cartilage tissues created by hMSCs with different conditions were implanted into osteochondral defect in rats. The results indicated that the tissue formed under hypoxic condition and induced with IGF1-supplemented chondrogenic medium displayed the best reparative results with minimal hypertrophy level. Our results demonstrate a new method to generate hyaline cartilage-like tissue from hMSCs without using exogenous scaffolds, which further pave the road for the clinical application of hMSC-based cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: In this study, hyaline cartilage-like tissues were generated from human mesenchymal stromal cells (hMSCs), which displayed robust capacity in repairing the osteochondral defect in rats. In particular, the extracellular matrix created by hMSCs was used, so no exogenous scaffold was needed. Through a series of optimization, we defined that hypoxic culture and supplementation of insulin-like growth factor-1 (IGF-1) in chondrogenic medium resulted in robust cartilage formation with minimal hypertrophy. We also demonstrated that hypoxic culture suppressed chondrogenesis and hypertrophy through modulating the Wnt/ß-catenin and IGF1 pathways, respectively. Our results demonstrate a new method to generate hyaline cartilage-like tissue from hMSCs without using exogenous scaffolds, which will further pave the road for the clinical application of hMSCs-based cartilage tissue engineering.

Influence of high-heeled shoe parameters on biomechanical performance of young female adults during stair ascent motion.

BACKGROUND: High-heeled shoes are currently preferred by women due to contemporary aesthetics. However, high-heeled shoes may increase the effort required to ascend stairs and, hence, alter biomechanical performance. RESEARCH QUESTION: How do high-heel shoe parameters affect the pelvis position, lower extremities kinematics, and ground reaction force in young women during stair ascent motion? METHODS: Stair ascent experiments were performed with 20 healthy adult women. The participants were instructed to ascend a 3-step staircase, wearing heeled shoes of different heel heights and heel types and one pair of flat shoes as the control group. Changes in lower body biomechanics were analyzed with kinematics and ground reaction force variables collected from the dominant limb. A two-way repeated ANOVA was performed to determine which variables were affected by heel type and which were affected by heel height or a combination of both. RESULTS: As the heel height increased, an increased range of ankle dorsiflexion-plantarflexion, as well as pelvic rotation, was observed(P = 0.039 and P = 0.003, respectively). A thinner heel type displayed a larger pelvic forward tilt movement(P = 0.026)and 1st peak vertical force(P = 0.025), as well as a smaller 2nd peak vertical force (P = 0.002). With high heels, increased external rotation of the knee, inversion and plantar flexion, and flexion values of the knee were observed. We also observed decreased external rotation of the pelvis, ankle eversion, varum, and dorsiflexion. SIGNIFICANCE: To stabilize body posture during stair ascent motion with high-heeled shoes, compensatory response including increasd pelvic range of motion and changing the joint angles of the lower extremities.

Influences of high-heeled shoe parameters on gait cycle, center of pressure trajectory, and plantar pressure in young females during treadmill walking.

PURPOSE: This study aimed to investigate the influences of high-heeled shoe (HHS) parameters on gait cycle, center of pressure (COP) trajectory, and plantar pressure in young females. METHODS: Twenty healthy adult females were recruited to participate in this study. Subjects walked on a treadmill at a fixed speed (1 m/s). Overall, six pairs of HHSs were evaluated, presenting two heel types (thin and thick) and three different heel heights (low: 3 cm, medium: 6 cm, and high: 8.2 cm). Subjects also wore flat shoes (heel height: 0.2 cm) as the control group. RESULTS: The gait cycle, COP parameters, peak pressure (PP), maximum force, contact area (CA), and force-time integral (impulse) were measured. The comparison between these parameters when the volunteers wore thick heel and flat shoes at different walking conditions indicated that thin heels caused a significant increase in the pre-swing parameter, CA, and PP of the first toe and first metatarsus. Increased heel heights yielded smaller gait line lengths, single support lines, and smaller hindfoot areas. By contrast, increased anterior-posterior positions and plantar pressure parameter values were noted for the forefoot. CONCLUSIONS: Data analyses showed significant differences in the plantar pressure distribution associated with heel height and heel type at increased pressure in the first metatarsal and central forefoot region and decreased pressure in the midfoot and heel sections, thus increasing anterior shift. The results presented herein may allow for the design of HHSs with reduced adverse health effects on the wearer.

Enamel-inspired materials design achieving balance of high stiffness and large energy dissipation.

Owing to the unique non-self-similar hierarchical microstructure, enamel achieves the balance of high stiffness and toughness, and in turn provides important ideas for the bio-inspired materials design. In this study, a multiscale numerical study has been conducted to investigate whether the property of high stiffness and large energy dissipation could be duplicated in engineering materials through certain material design principles. Motivated by the structure of enamel, the bio-inspired materials consisting of hard and soft phases were considered, and the designing parameters including the cross-sectional shape, volume fraction, and inclination angle of the reinforcement, and other three parameters related to the waviness of the reinforcement were taken into account. It was found that by employing the non-self-similar hierarchical structure, the designed composites exhibited the balance between stiffness and toughness, which has not been achieved in many engineering materials yet. Furthermore, the influences of the aforementioned designing parameters on the mechanical performance of the composites have been elucidated. The findings of this study have provided a guideline for designing bio-inspired composites achieving the balance between stiffness and toughness.

Aneurysmal bone cyst of the metatarsal: A case report.

An aneurysmal bone cyst (ABC) is a rare, non-neoplastic, destructive, hemorrhagic and expansile lesion accounting for 1% of all bone tumors. This type of lesion predominantly affects long bones and vertebrae. ABC of the metatarsal is rare and only a few cases have been reported in the literature to date. The present study reports a rare case of ABC of the third metatarsal occurring in a 27-year-old male patient, who presented with repeated foot swelling that had lasted for ~1 year. Other clinical manifestations included limping, multiple lumps (defined as masses on or below the skin, as detected by imageological diagnosis) and progressively increasing local pain in his right foot. Magnetic resonance imaging of the right metatarsal revealed a segmented, expansile, multiseptated lesion with fluid-fluid levels. An en bloc resection was performed and the defect was replaced with a tricortical iliac autograft. Pathological analysis of the resected tissue suggested ABC. The present study aims to describe a case of ABC of the metatarsal, a condition that often poses a diagnostic challenge, and to underline the importance of radiological and histological examinations for the accuracy of that diagnosis.

Synovial lipomatosis of the metatarsophalangeal joint: A case report.

Synovial lipomatosis, also termed lipoma arborescens, is an extremely rare disorder of the synovium that causes joint pain, swelling and effusion. To date, only a small number of cases have been reported in the literature. The current study presents the case of a 44-year-old male with repeated swelling of the metatarsophalangeal joints of the left hallux, which had persisted for ~3 years. The main clinical manifestations on presentation included multiple osseous lumps and limited activity of the left hallux without pain. Magnetic resonance imaging of the left hallux revealed a mass surrounding the left metatarsophalangeal joints. Subsequently, the lesion was resected. Pathological examination revealed well-defined lobules of mature adipocytes separated by thin fibrous septa, which indicated a diagnosis of synovial lipomatosis of the metatarsophalangeal joint of the left foot. The aim of this study was to evaluate synovial lipomatosis of the metatarsophalangeal joint, with an analysis of the clinical parameters and pathological features of the disorder.

Inhibitory Effects of Lanthanum Chloride on Wear Particle-Induced Osteolysis in a Mouse Calvarial Model.

Osteolysis is a bone disorder associated with progressive destruction of bone tissues. However, the effects of lanthanum chloride (LaCl3) on osteolysis remain unknown. Therefore, the aim of this study was to determine the effects of LaCl3 on osteolysis in vivo. In a mouse calvarial model, C57BL/6J mice were injected with wear particles with or without LaCl3. Microcomputed tomography, hematoxylin and eosin staining, and tartrate-resistant acid phosphatase staining were performed for the pathological characterization of calvariae, and eight calvariae per group were prepared for the assay of TNF-α, IL-1ß, and RANKL secretion using quantitative enzyme-linked immunosorbent assay (ELISA). In mice treated with high-dose LaCl3, particle-induced osteolysis and inflammatory reaction were reduced compared with that in the vehicle-treated control. Moreover, treatment with high-dose LaCl3 suppressed the wear particle-induced decrease in bone mineral content, bone mineral density, and bone volume fraction. Bone destruction and resorption were higher in the LaCl3-treated group than in the saline-treated group but lower than those in the wear particle group. Finally, our results showed that treatment with a high dose of LaCl3 suppressed osteoclastogenesis. Thus, LaCl3 may represent a novel therapeutic agent for the treatment or prevention of wear particle-induced osteolysis and aseptic loosening.

Lanthanum Chloride Attenuates Osteoclast Formation and Function Via the Downregulation of Rankl-Induced Nf-κb and Nfatc1 Activities.

The biological activities of lanthanum chloride (LaCl3 ) and the molecular mechanisms of action underlying its anti-inflammatory, anti-hyperphosphatemic, and osteoblast-enhancing effects have been studied previously, but less is known about the effects of LaCl3 on osteoclasts. The present study used in vivo and in vitro approaches to explore the effects of LaCl3 on osteoclasts and osteolysis. The results indicated that LaCl3 concentrations that were non-cytotoxic to mouse bone marrow-derived monocytes attenuated receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis, bone resorption, mRNA expression of osteoclastogenic genes in these cells, including cathepsin K, calcitonin receptor, and tartrate-resistant acid phosphatase (TRAP). Further, LaCl3 inhibited RANKL-mediated activation of the nuclear factor-κB (NF-κB) signaling pathway, and downregulated mRNA and protein levels of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), and c-fos. In vivo, LaCl3 attenuated titanium (Ti) particle-induced bone loss in a murine calvarial osteolysis model. Histological analyses revealed that LaCl3 ameliorated bone destruction and decreased the number of TRAP-positive osteoclasts in this model. These results demonstrated that LaCl3 inhibited osteoclast formation, function, and osteoclast-specific gene expression in vitro, and attenuated Ti particle-induced mouse calvarial osteolysis in vivo, where the inhibition of NF-κB signaling and downregulation of NFATc1 and c-fos played an important role.