Porous tantalum rod implantation is associated with low survival rates in patients with type C2 osteonecrosis of the femoral head but has no effect on the clinical outcome of conversion total hip arthroplasty: a retrospective study with an average 8-year follow-up.

BACKGROUND: Our study aimed to investigate the clinical outcomes and survival rates following porous tantalum rod surgery (PTRS) and conversion total hip arthroplasty (THA) subsequent to failed PTRS. METHODS: A total of 38 subjects (40 hips) with osteonecrosis of the femoral head (ONFH) were included in this retrospective study between January 2008 and December 2011. All subjects were evaluated before surgery by using the Association Research Circulation Osseous (ARCO) classification system, the Japan Investigation Committee (JIC) classification and the Harris hip score (HHS). The endpoint of this study was set as final follow-up (including the survival time of PTRS and conversion THA). The rates of radiological progression were also evaluated. Patients who received conversion THA were further followed and compared to a control group of 58 patients with ONFH who underwent primary THA. RESULTS: The mean follow-up time was 120.7 ± 9.2 (range, 104-143) months, and the overall survival rate was 75% at 96 months (ARCO stage II: 81.5%; stage III: 38.5%; JIC type C1: 83.3%; C2: 30%). The HHS before surgery was 59 (55-61), in contrast to 94 (91-96) at 96 months follow-up (P < 0.01). HHS in stage III show a significant poorer result compared to stage II at 24 months. HHS in Type C2 group show no significant difference compared to HHS before surgery at 24 and 60 months follow up (P = 0.91, P = 0.30). Twelve hips requiring secondary THA were followed for 66.9 ± 31.7 months, and control hips that underwent primary THA was followed for 75.4 ± 14.9 months. The HHS in the conversion group was 89 (86-93) and that in the primary THA group was 92 (79-95, P = 0.09) at the 5-year follow-up. CONCLUSION: In the mid-term follow-up, porous tantalum implants showed an encouraging survival rate in symptomatic patients in early stages (ARCO stage II) or with limited necrotic lesions (JIC type C1). In addition, our results did not demonstrated any difference between primary THA and conversion THA.

Functional disuse initiates medullary endosteal micro-architectural impairment in cortical bone characterized by nanoindentation.

In this study, we evaluated the effect of functional disuse-induced bone remodeling on its mechanical properties, individually at periosteum and medullary endosteum regions of the cortical bone. Left middle tibiae were obtained from 5-month-old female Sprague-Dawley rats for the baseline control as well as hindlimb suspended (disuse) groups. Micro-nano-mechanical elastic moduli (at lateral region) was evaluated along axial (Z), circumferential (C) and radial (R) orientations using nanoindentation. Results indicated an anisotropic microstructure with axial orientation having the highest and radial orientation with the lowest moduli at periosteum and medullary endosteum for both baseline control as well as disuse groups. Between the groups: at periosteum, an insignificant difference was evaluated for each of the orientations (p > 0.05) and at endosteum, a significant decrease of elastic moduli in the radial (p < 0.0001), circumferential (p < 0.001) and statistically insignificant difference in axial (p > 0.05) orientation. For the moduli ratios between groups: at periosteum, only significant difference in the Z/R (p < 0.05) anisotropy ratio, whereas at endosteum, a statistically significant difference in Z/C (p < 0.001), and Z/R (p < 0.001), as well as C/R (p < 0.05) anisotropy ratios, was evaluated. The results suggested initial bone remodeling impaired bone micro-architecture predominantly at the medullary endosteum with possible alterations in the geometric orientations of collagen and mineral phases inside the bone. The findings could be significant for studying the mechanotransduction pathways involved in maintaining the bone micro-architecture and possibly have high clinical significance for drug use against impairment from functional disuse.

Engineered nanomedicine for neuroregeneration: light emitting diode-mediated superparamagnetic iron oxide-gold core-shell nanoparticles functionalized by nerve growth factor.

This paper reports nerve growth factor functionalized superparamagnetic iron oxide-gold core-shell nanoparticles (NGF-SPIO-Au NPs), an engineered nanomedicine for non-invasive neuron regeneration when irradiated by a low-intensity light-emitting diode (LED). NGF-SPIO-Au NPs of 20 µg/ml, were tested on PC-12 neuron-like cells, irradiated by LEDs (525 nm, 1.09, 1.44, and 1.90 mW/cm2). A remarkable Ca2+ influx was detected in differentiated PC-12 cells treated with NPs, irradiated by LED of 1.90 and 1.44 mW/cm2 with great cell viability (>84%) and proliferations. The strong heat generated through their plasmonic surface upon LED irradiation on NGF-SPIO-Au NPs was observed. For cells treated with LED (1.90 mW/cm2) and NGF-SPIO-Au NPs, a dramatic enhancement of neuronal differentiation (83%) and neurite outgrowth (51%) was found, and the upregulation of both the neural differentiation specific marker (ß3-tubulin) and the cell adhesive molecule (integrin ß1) was observed by the reverse transcription-polymerase chain reaction and western blot analysis.

A Biomechanical Comparison of Alternative Graft Preparations for All-Inside Anterior Cruciate Ligament Reconstruction.

PURPOSE: To biomechanically compare alternative graft constructs for all-inside anterior cruciate ligament (ACL) reconstruction in the event that the semitendinosus harvested is too narrow or too short to make a graft larger than 8 mm. METHODS: Bovine extensor tendons were used to make 6 different 9-mm-diameter grafts: traditional 4-strand, anastomosis 4-strand, 6-strand, 3-strand, button-fixation 4-strand, and loop-and-tack 4-strand grafts. The grafts were then subjected to cyclic biomechanical testing followed by failure loading. Force at 3 and 5 mm of displacement and ultimate force were recorded for all grafts. RESULTS: Compared with the traditional 4-strand graft, the only graft that showed significant biomechanical differences during the cyclic phase of testing was the button-fixation 4-strand graft, which was characterized by lower force at 3 mm of displacement (74 ± 34 N vs 122 ± 13 N, P = .004) and 5 mm of displacement (122 ± 35 N vs 172 ± 3 N, P = .006). During failure loading, ultimate force was significantly lower for both the 6-strand graft (491 ± 186 N, P = .041) and button-fixation 4-strand graft (326 ± 27 N, P < .001) than for the traditional 4-strand graft (778 ± 176 N). All other grafts were equivalent for the parameters tested. CONCLUSIONS: The anastomosis 4-strand, 3-strand, and loop-and-tack 4-strand grafts do not biomechanically differ in cyclic loading and ultimate force from traditional 4-strand grafts. This study supports the use of anastomosis 4-strand, 3-strand, or loop-and-tack 4-strand grafts in the event that a traditional all-inside 4-strand graft cannot be prepared from a harvested semitendinosus tendon in ACL reconstruction. CLINICAL RELEVANCE: This study tests and describes alternatives to the traditional 4-strand semitendinosus autograft for all-inside ACL reconstruction in the event that the harvested tendon is not adequate.

Zinc regulates vascular endothelial cell activity through zinc-sensing receptor ZnR/GPR39.

Zn2+ is an essential element for cell survival/growth, and its deficiency is linked to many disorders. Extracellular Zn2+ concentration changes participate in modulating fundamental cellular processes such as proliferation, secretion, ion transport, and cell signal transduction in a mechanism that is not well understood. Here, we hypothesize that the Zn2+-sensing receptor ZnR/G protein-coupled receptor 39 (GPR39), found in tissues where dynamic Zn2+ homeostasis takes place, enables extracellular Zn2+ to trigger intracellular signaling pathways regulating key cell functions in vascular cells. Thus, we investigated how extracellular Zn2+ regulates cell viability, proliferation, motility, angiogenesis, vascular tone, and inflammation through ZnR/GPR39 in endothelial cells. Knockdown of GPR39 through siRNA largely abolished Zn2+-triggered cellular activity changes, Ca2+ responses, as well as the downstream activation of Gαq-PLC pathways. Extracellular Zn2+ promoted vascular cell survival/growth through activation of cAMP and Akt as well as overexpressing of platelet-derived growth factor-α receptor and vascular endothelial growth factor A. It also enhanced cell adhesion and mobility, endothelial tubule formation, and cytoskeletal reorganization. Such effects from extracellular Zn2+ were not observed in GPR39-/- endothelial cells. Zn2+ also regulated inflammation-related key molecules such as heme oxygenase-1, selectin L, IL-10, and platelet endothelial cell adhesion molecule 1, as well as vascular tone-related prostaglandin I2 synthase and nitric oxide synthase-3. In sum, extracellular Zn2+ regulates endothelial cell activity in a ZnR/GPR39-dependent manner and through the downstream Gαq-PLC pathways. Thus, ZnR/GPR39 may be a therapeutic target for regulating endothelial activity.

Promoting neuroregeneration by applying dynamic magnetic fields to a novel nanomedicine: Superparamagnetic iron oxide (SPIO)-gold nanoparticles bounded with nerve growth factor (NGF).

Neuroregeneration imposes a significant challenge in neuroscience for treating neurodegenerative diseases. The objective of this study is to evaluate the hypothesis that the nerve growth factor (NGF) functionalized superparamagnetic iron oxide (SPIO)-gold (Au) nanomedicine can stimulate the neuron growth and differentiation under external magnetic fields (MFs), and dynamic MFs outperform their static counterparts. The SPIO-Au core-shell nanoparticles (NPs) (Diameter: 20.8 nm) possessed advantages such as uniform quasi-spherical shapes, narrow size distribution, excellent stabilities, and low toxicity (viability >96% for 5 days). NGF functionalization has enhanced the cellular uptake. The promotion of neuronal growth and orientation using NGF functionalized SPIO-Au NPs, driven by both the static and dynamic MFs, was revealed experimentally on PC-12 cells and theoretically on a cytoskeletal force model. More importantly, dynamic MFs via rotation performed better than the static ones, i.e., the cellular differentiation ratio increased 58%; the neurite length elongation increased 63%.

Association of reduced sclerostin expression with collapse process in patients with osteonecrosis of the femoral head.

PURPOSE: Sclerostin is an osteocyte-derived protein that has a potent inhibitory effect on osteoblast activity. The osteocyte apoptosis induced by various causes of osteonecrosis of the femoral head (ONFH) plays a key role in the promotion of femoral head collapse. But the effect of altering sclerostin level on the collapse of ONFH has not been studied. Our aim was to assess the role of sclerostin level in the collapse of ONFH. METHODS: Between May 2016 and November 2016, 236 subjects were enrolled in the present study. The patients were classified according to the Association Research Circulation Osseous (ARCO) classification. The clinical bone histomorphology, the expression position, and level of sclerostin as well as the plasma sclerostin level were evaluated. RESULTS: The sclerostin level was significantly lower in the non-traumatic ONFH group than those in the healthy control group (P = 0.002). The sclerostin level was negatively associated with ARCO stages (r = - 0.239, P = 0.009) and significantly lower in the postcollapse group (P = 0.025). CONCLUSIONS: The reduced expression of sclerostin may play a key role in the collapse process of ONFH and be predictive of the disease progression of ONFH.

SHP2 regulates osteoclastogenesis by promoting preosteoclast fusion.

Genes that regulate osteoclast (OC) development and function in both physiologic and disease conditions remain incompletely understood. Shp2 (the Src homology-2 domain containing protein tyrosine phosphatase 2), a ubiquitously expressed cytoplasmic protein tyrosine phosphatase, is implicated in regulating M-CSF and receptor activator of nuclear factor-κB ligand (RANKL)-evoked signaling; its role in osteoclastogenesis and bone homeostasis, however, remains unknown. Using a tissue-specific gene knockout approach, we inactivated Shp2 expression in murine OCs. Shp2 mutant mice are phenotypically osteopetrotic, featuring a marked increase of bone volume (BV)/total volume (TV) (+42.8%), trabeculae number (Tb.N) (+84.1%), structure model index (+119%), and a decrease of trabecular thickness (Tb.Th) (-34.1%) and trabecular spacing (Tb.Sp) (-41.0%). Biochemical analyses demonstrate that Shp2 is required for RANKL-induced formation of giant multinucleated OCs by up-regulating the expression of nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1), a master transcription factor that is indispensable for terminal OC differentiation. Shp2 deletion, however, has minimal effect on M-CSF-dependent survival and proliferation of OC precursors. Instead, its deficiency aborts the fusion of OC precursors and formation of multinucleated OCs and decreases bone matrix resorption. Moreover, pharmacological intervention of Shp2 is sufficient to prevent preosteoclast fusion in vitro. These findings uncover a novel mechanism through which Shp2 regulates osteoclastogenesis by promoting preosteoclast fusion. Shp2 or its signaling partners could potentially serve as pharmacological targets to regulate the population of OCs locally and/or systematically, and thus treat OC-related diseases, such as periprosthetic osteolysis and osteoporosis.

Dynamic fluid flow induced mechanobiological modulation of in situ osteocyte calcium oscillations.

Distribution of intramedullary pressure (ImP) induced bone fluid flow has been suggested to influence the magnitude of mechanotransductory signals within bone. As osteocytes have been suggested as major mechanosensors in bone network, it is still unclear how osteocytes embedded within a mineralized bone matrix respond to the external mechanical stimuli derived from direct coupling of dynamic fluid flow stimulation (DFFS). While in vitro osteocytes show unique Ca(2+) oscillations to fluid shear, the objective of this study was to use a confocal imaging technique to visualize and quantify Ca(2+) responses in osteocytes in situ under DFFS into the marrow cavity of an intact ex vivo mouse femur. This study provided significant technical development for evaluating mechanotransduction mechanism in bone cell response by separation of mechanical strain and fluid flow factors using ImP stimulation, giving the ability for true real-time imaging and monitoring of bone cell activities during the stimulation. Loading frequency dependent Ca(2+) oscillations in osteocytes indicated the optimized loading at 10Hz, where such induced response was significantly diminished via blockage of the Wnt/ß-catenin signaling pathway. The results provided a pilot finding of the potential crosstalk or interaction between Wnt/ß-catenin signaling and Ca(2+) influx signaling of in situ osteocytes in response to mechanical signals. Findings from the present study make a valuable tool to investigate how in situ osteocytes respond and transduce mechanical signals, e.g. DFFS, as a central mechanosensor.

Observation of sGAG content of human hip joint cartilage in different old age groups based on EPIC micro-CT.

OBJECTIVES: To observe the age-related changes of sulfated glycosaminoglycan (sGAG) content of hip joint cartilage of elderly people based on Equilibrium Partitioning of an Ionic Contrast Agent (EPIC) micro-CT. METHODS: Seventy human hip cartilage-bone samples were collected from hip-fracture patients (ages 51-96) and divided into five groups (10 years in an age group). They were first immersed in 20% concentration of the contrast agent Meglumine Diatrizoate (MD) for 6 h at 37 °C, and then scanned by micro-CT. Following scanning, samples were stained for sGAG with toluidine blue. The X-ray attenuation and sGAG optical density were calculated by image processing. The correlation between X-ray attenuation and sGAG optical density was then analyzed. RESULTS: The X-ray mean attenuation of the cartilage increased by 18.81% from the 50-80 age groups (p < 0.01), but decreased by 7.15% in the 90 age group compared to the 80 age group. The X-ray mean attenuation of the superficial layer and middle layer increased by 31.60 % and 44.68% from the 50-80 age groups, respectively (p < 0.01), but reduced by 4.67% and 6.05% separately in the 90 age group. However, the deep layer showed no significant change with aging. The sGAG optical density showed a linear correlation (r = -0.91, p < 0.01) with the X-ray attenuation. CONCLUSION: The sGAG content of hip joint cartilage varied with aging in elderly people. The changes in superficial layer and middle layer were more evident than deep layer.