Mid-vastus total knee arthroplasty for medial osteoarthritis recovers gait balance control better than lateral parapatellar approach three months post-surgery.

Total knee arthroplasty (TKA) approaches affect recovery outcomes, with different levels of residual loss of muscle strength and functional deficits. The current study compared the gait balance control in older individuals 3 months after TKA via the lateral parapatellar approach (LPPA) and mid-vastus approach (MVA) in terms of the inclination angle (IA) of the center of pressure (COP) to the body's center of mass (COM) vector, and the rate of change of IA (RCIA). In a gait laboratory, 12 patients with severe medial knee osteoarthritis who had undergone bilateral TKA via LPPA and 12 via MVA were evaluated and compared against 12 healthy controls for their balance control during gait 3 months after surgery. The participants' kinematic data and ground reaction forces were measured synchronously using an 8-camera motion capture system and three forceplates, respectively, from which the COM, COP, IA and RCIA were calculated using a 13-body-segment model. The LPPA group showed significantly greater sagittal IA during DLS (p < 0.01) but less sagittal and frontal RCIA throughout the gait cycle (p < 0.04) compared to controls. The MVA showed better recovery in the balance control with most IA and RCIA variables similar to those of the healthy controls throughout the gait cycle. The patients with LPPA walked with a compromised balance control throughout the gait cycle while the MVA group showed close-to-normal balance control with a slight decrease in sagittal RCIA during SLS. The current between-approach findings were likely related to the differences in the muscles involved during surgery, suggesting that MVA may be a better choice than LPPA when taking short-term gait balance control into consideration.

Recovery of balance control in bilateral medial knee osteoarthritis after total knee arthroplasty during level walking.

Older adults are at higher risk of falling following total knee arthroplasty (TKA). However, it remains unclear how long a full recovery of the balance control during gait post-TKA will take. The current study aimed to bridge this knowledge gap via long-term follow-up gait analyses. Twelve older adults with severe bilateral medial knee osteoarthritis (OA) before, 3 and 12 months after TKA, and twelve healthy controls were evaluated for their balance control during level walking, in terms of the inclination angle (IA) of the center of pressure to center of mass vector, and the rate of change of IA (RCIA). The patients before TKA showed significantly increased sagittal IA but decreased RCIA throughout the gait cycle (p < 0.04) compared to controls, suggesting a compromised balance control. Three months post-TKA, deviations in IA remained, although those in RCIA were improved to normal. One-year post-TKA, no significant differences were found in any of the IA- and RCIA-related variables between patient and Control groups. The results show that TKA surgery was effective in reducing the deviations in the center of mass-center of pressure control in patients with severe bilateral knee OA, and full recovery of balance control can be expected 1 year after surgery.

Safety and Efficacy of Kartigen® in Treating Cartilage Defects: A Randomized, Controlled, Phase I Trial.

Here, we aimed to investigate the safety and preliminary efficacy of Kartigen®, a matrix with autologous bone marrow mesenchymal stem cell-derived chondrocyte precursors embedded in atelocollagen. As a surgical graft, Kartigen® was implanted onto the cartilage defects at the weight-bearing site of the medial femoral condyle of the knee. Fifteen patients were enrolled and stratified into two groups, undergoing either Kartigen® implantation (n = 10) or microfracture (control group, n = 5). The primary endpoint was to evaluate the safety of Kartigen® by monitoring the occurrence of adverse events through physician queries, physical examinations, laboratory tests, and radiological analyses for 2 years. There were no infections, inflammations, adhesions, loose body, or tumor formations in the Kartigen®-implanted knees. The preliminary efficacy was assessed using the International Knee Documentation Committee (IKDC) score, visual analog scale, and second-look arthroscopy. The postoperative IKDC scores of the Kartigen® group significantly improved in the 16th week (IKDC = 62.1 ± 12.8, p = 0.025), kept increasing in the first year (IKDC = 78.2 ± 15.4, p < 0.005), and remained satisfactory in the second year (IKDC = 73.6 ± 13.8, p < 0.005), compared to the preoperative condition (IKDC = 47.1 ± 17.0), while the postoperative IKDC scores of the control group also achieved significant improvement in the 28th week (IKDC = 68.5 ± 6.1, p = 0.032) versus preoperative state (IKDC = 54.0 ± 9.1). However, the IKDC scores decreased in the first year (IKDC = 63.5 ± 11.6) as well as in the second year (IKDC = 52.6 ± 16.4). Thirteen patients underwent second-look arthroscopy and biopsy one year after the operation. The Kartigen® group exhibited integration between Kartigen® and host tissue with a smooth appearance at the recipient site, whereas the microfracture group showed fibrillated surfaces. The histological and immunohistochemical analyses of biopsy specimens demonstrated the columnar structure of articular cartilage and existence of collagen type II and glycosaminoglycan mimic hyaline cartilage. This study indicates that Kartigen® is safe and effective in treating cartilage defects.

Recommendations for psoriatic arthritis management: A joint position paper of the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology.

In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.

Protective effects of aucubin on osteoarthritic chondrocyte model induced by hydrogen peroxide and mechanical stimulus.

BACKGROUND: During the onset of osteoarthritis (OA), certain biochemical events have been shown to accelerate cartilage degradation, including the dysregulation of cartilage ECM anabolism, abnormal generation of reactive oxygen species (ROS) and overproduction of proteolytic enzymes and inflammatory cytokines. The potency of aucubin in protecting cellular components against oxidative stress, inflammation and apoptosis effects are well documented, which makes it a potential candidate for OA treatment. In this study, we aimed to evaluate the protective benefits of aucubin against OA using H2O2 and compression induced OA-like chondrocyte models. METHODS: The effects of aucubin were studied in porcine chondrocytes after 1 mM H2O2 stimulation for 30 min or sustained compression for 24 h. Effects of aucubin on cell proliferation and cytotoxicity of chondrocytes were measured with WST-1 and LDH assays. ROS production was evaluated by the Total ROS/Superoxide Detection Kit. Caspase-3 activity was evaluated by the CaspACE assay system. The levels of apoptosis were evaluated by the Annexin V-FITC apoptosis detection kit. OA-related gene expression was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Total DNA quantification was evaluated by the DNeasy Blood and Tissue kit. Sulfated-glycosaminoglycans (sGAGs) production and content were evaluated by DMMB assay and Alcian blue staining. RESULTS: The results showed that the ROS scavenge effects of aucubin appeared after 1 h of pretreatment. Aucubin could reduce the caspase-3 activity induced by H2O2, and reduced the apoptosis cell population in flowcytometry. In RT-qPCR results, aucubin could maintain ACAN and COL2A1 gene expressions, and prevent IL6 and MMP13 gene up-regulation induced by H2O2 and compression stimulations. In the DMMB assay and Alcian blue staining, aucubin could maintain the sGAG content and protect chondrocytes against compressive stress, but not oxidative stress from H2O2. CONCLUSIONS: These results indicated that aucubin has protective effects in an osteoarthritic chondrocyte model induced by H2O2 and mechanical stimulus.

An assessment of femoral rotational alignment of mini-incision total knee arthroplasty: A comparison based on the transepicondylar line from the kneeling view and the intraoperative posterior condylar line.

BACKGROUND: Rotational alignment of the distal femur is important in total knee arthroplasty. The purpose of this study is to use a roentgenographic technique to evaluate the accuracy of mini-incision total knee arthroplasty (MIS TKA) performed based on the transepicondylar line from the kneeling view. METHODS: Totally 32 patients (aged from 64 to 80 years with an average of 70.9 years) with 46 cases of knee osteoarthritis received MIS TKA were registered. Before surgery, the condylar twist angle was measured from the kneeling view. The bone cut for the external rotation was completed, with regard to the condylar twist angle. The control group including 26 patients (aged from 50 to 89 years with an average of 69.7 years) with 42 cases of knee osteoarthritis underwent TKA with built-in cutting jig design 3 degrees of femoral external rotation. This study is a prospective continuous-time duration analysis study. The level of evidence is IIc. RESULTS: The mean condylar twist angle was 5.1° in the experimental group and 5.4° in the control group. The mean postoperative angle between the clinical epicondylar axis and the posterior condylar line of the femoral component was 0.46°. The same postoperative angle of the built-in external rotation in the control group was 2.7°. The condylar twist angle was significantly more accurate than the built-in design. CONCLUSION: Our result substantiates that the kneeling view is practicable and reproducible as the cutting reference for femoral external rotation. The accuracy of the kneeling view shows that the epicondylar axis can be used in smaller wound surgery, such as MIS TKA. LEVEL OF EVIDENCE: Level IIc.

Drynaria fortunei J. Sm. improves the bone mass of ovariectomized rats through osteocalcin-involved endochondral ossification.

AIM OF THIS STUDY: Our previous study showed that Drynaria fortunei J. Sm. (Kunze), a traditional Chinese medical herb, can promote osteoblast differentiation and maturation. This study was further aimed to confirm the traditional effects of Kunze on the bone mass of ovariectomized rats. MATERIALS AND METHODS: Female Wistar rats were given an ovariectomy and then administered the water extract of Kunze (WEK). Systemic and tissue toxicities of WEK were assessed. A biomechanical test, bone mineral contents, and bone histomorphometry were analyzed to determine the effects of the WEK on the bone mass. Levels of osteocalcin (OCN) in bone tissues were determined by immunohistochemistry and immunoblotting. The effects of naringin, one of the bioactive compounds of the WEK, on the bone mass were evaluated. RESULTS: A bilateral ovariectomy in rats caused a time-dependent decrease in levels of serum 17ß-estradiol. Exposure of ovariectomized rats to the WEK at 0.5 and 1g/kg body weight/day for 1, 2, 3, and 6 months did not induce systemic or tissue toxicities. Biomechanical testing and a bone mineral content analysis showed that the ovariectomy decreased the bone torsion force and bone ash in time-dependent manners. In comparison, after exposure to the WEK, the ovariectomy-induced reductions in the bone torsion force and bone ash were significantly alleviated. In parallel, results of a bone histomorphometric assay further revealed that the ovariectomy caused significant diminution in the production of prehypertrophic chondrocytes and trabecular bone but enhanced hypertrophic chondrocyte numbers in the growth plate. However, exposure to the WEK lowered ovariectomy-induced changes in these cellular events. As to the mechanism, the WEK increased OCN biosynthesis in bone tissues of ovariectomized rats. Administration of naringin to ovariectomized rats caused significant amelioration of the bone strength, bone mineral contents, and trabecular bone amounts. CONCLUSIONS: This study shows that the WEK can translationally promote the bone mass in ovariectomized rats through stimulating OCN-involved endochondral ossification.

Cartilage regeneration in SCID mice using a highly organized three-dimensional alginate scaffold.

Tissue engineering for cartilage regeneration provides an alternative to surgery for degenerative osteoarthritis. Recently, a highly organized three-dimensional (3D) alginate scaffold was prepared using a microfluidic device; this scaffold is effective for chondrocyte culture in vitro. The performance of this scaffold was further demonstrated; an alginate scaffold seeded with porcine chondrocytes was implanted in the dorsal subcutaneous site of SCID mice. The recipients were sacrificed at 2, 4, and 6 weeks after transplantation. The grafted implants retrieved from the subcutaneous site were analyzed with histologic examinations. Real-time PCR was used to identify the gene expression patterns of the chondrocytes. The hematoxylin and eosin staining showed that the chondrocytes survived normally in SCID mice; cartilage-like structures were formed after 4 weeks implantation. Immunohistochemical staining revealed cells secreted type II collagen, produced glycosaminoglycans (proved by alcian blue stain), and maintained the expression of S-100. On the other hand, the cells were negative for type I and type X collagen staining. PCR showed that the mRNA expressions of aggrecan and type II collagen were up-regulated at weeks two and four, while type I and type X collagen were down-regulated during the study period. In summary, this highly organized 3D alginate scaffold provided a suitable environment and maintained functional phenotypes for chondrocytes in this animal study.

Cognitive stimulation during hospitalization improves global cognition of older Taiwanese undergoing elective total knee and hip replacement surgery.

AIM: This article is a report on a pilot study conducted to determine the effects of cognitively stimulating activities in older patients undergoing elective hip and/or knee replacement. BACKGROUND: Cognitive decline occurs in 16-35·5% of older hospitalized patients. In-hospital interventions, such as cognitively stimulating activities, might combat cognitive decline. However, evidence supporting such interventions is limited. METHODS: For this randomized pilot trial, 50 older patients (90% women with a mean age of 72·8 years) were recruited in 2008 from a tertiary medical centre in Taiwan. While hospitalized, participants in the intervention group received a daily nurse-led, individual-based, cognitive-stimulation intervention. The comparison group received usual care. Cognitive function was assessed using Mini-Mental State Examination at admission, discharge and 1 month after discharge. RESULTS: The incidence of cognitive decline (≥2-point decline in cognitive score) by hospital discharge was significantly lower for the intervention group (12%) than the usual care group (44%). The intervention group also had better cognitive scores following hospitalization. Upon discharge, participants in the intervention group scored 1·28 points higher than at admission, whereas participants in the usual care declined by 0·76 points. Improvement in cognitive status persisted for the intervention group (+1·33 points) vs. usual care (-0·26 points) at 1 month after discharge. Group differences in changes were statistically significant both at discharge and 1 month afterwards. CONCLUSION: Our cognitive-stimulation intervention benefited global cognitive function among older patients undergoing elective hip and/or knee replacement. The benefit persisted at 1 month after discharge.

A mutation in cartilage oligomeric matrix protein (COMP) causes early-onset osteoarthritis in a large kindred study.

We performed a genome-wide linkage analysis to identify susceptibility loci in a large six-generation extended family previously reported with early-onset osteoarthritis (OA) DNA sequencing was performed to investigate involvement of the COMP (Cartilage oligomeric matrix protein) gene in this family. The region covering D19S884, D19S226, and D19S414 on chromosome 19p following genome-wide scan from 70 individuals of this kindred showed significant linkage, with a maximum point LOD (logarithm of the odds ratio) score of 2.51 at D19S226. Direct sequencing of the COMP gene, the most plausible candidate gene in the region, identified a c.2152C>T substitution in exon 18 which resulted in a substitution of tryptophan for arginine at position 718 located in the C terminal globular domain of the gene product. A total of 26 individuals were identified with this mutation of which 21 affected individuals had the mutation, and the other five younger individuals (18.6 ± 11.3 years of age) carried the mutation without symptoms. The results indicate that COMP is the disease susceptibility gene and the c.2152C>T mutation in exon 18 could cause early-onset OA phenotypes in this kindred, which is compatible with a previous report that this mutation also causes a mild form of multiple epiphyseal dysplasia (MED).

A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology.

Osteoarthritis is a degenerative disease and frequently involves the knee, hip and phalangeal joints. Current treatments used in small cartilage defects including multiple drilling, abrasion arthroplasty, mosaicplasty, and autogenous chondrocyte transplantation, however, there are problems needed to be solved. The standard treatment for severe osteoarthritis is total joint arthroplasty. The disadvantages of this surgery are the possibility of implant loosening. Therefore, tissue engineering for cartilage regeneration has become a promising topic. We have developed a new method to produce a highly organized single polymer (alginate) scaffold using microfluidic device. Scanning electron microscope and confocal fluoroscope examinations showed that the scaffold has a regular interconnected porous structure in the scale of 250 µm and high porosity. The scaffold is effective in chondrocyte culture; the cell viability test (WST-1 assay), cell toxicity (lactate dehydrogenase assay), cell survival rate, extracellular matrix production (glycosaminoglycans contents), cell proliferation (DNA quantification), and gene expression (real-time PCR) all revealed good results for chondrocyte culture. The chondrocytes can maintain normal phenotypes, highly express aggrecan and type II collagen, and secrete a great deal of extracellular matrix when seeded in the alginate scaffold. This study demonstrated that a highly organized alginate scaffold can be prepared with an economical microfluidic device, and this scaffold is effective in cartilage tissue engineering.

Tissue engineering-based cartilage repair with mesenchymal stem cells in a porcine model.

This in vivo pilot study explored the use of mesenchymal stem cell (MSC) containing tissue engineering constructs in repair of osteochondral defects. Osteochondral defects were created in the medial condyles of both knees of 16 miniature pigs. One joint received a cell/collagen tissue engineering construct with or without pretreatment with transforming growth factor ß (TGF-ß) and the other joint from the same pig received no treatment or the gel scaffold only. Six months after surgery, in knees with no treatment, all defects showed contracted craters; in those treated with the gel scaffold alone, six showed a smooth gross surface, one a hypertrophic surface, and one a contracted crater; in those with undifferentiated MSCs, five defects had smooth, fully repaired surfaces or partially repaired surfaces, and one defect poor repair; in those with TGF-ß-induced differentiated MSCs, seven defects had smooth, fully repaired surfaces or partially repaired surfaces, and three defects showed poor repair. In Pineda score grading, the group with undifferentiated MSC, but not the group with TGF-ß-induced differentiated MSCs, had significantly lower subchondral, cell morphology, and total scores than the groups with no or gel-only treatment. The compressive stiffness was larger in cartilage without surgical treatment than the treated area within each group. In conclusion, this preliminary pilot study suggests that using undifferentiated MSCs might be a better approach than using TGF-ß-induced differentiated MSCs for in vivo tissue engineered treatment of osteochondral defects.

Clinical result of sintered bovine hydroxyapatite bone substitute: analysis of the interface reaction between tissue and bone substitute.

BACKGROUND: Autogenic bone graft is the first choice for managing bone defects. However, donor site-associated morbidity and limited bone volume are constraints in clinical applications. Allografts can provide sufficient amounts for bone defects but have a high risk of infection. Bone substitute composed of hydroxyapatite (HA) is an alternative material for avoiding the aforementioned risks. Sintered bovine bone is a naturally occurring HA that has been proved to have excellent bioactivity for inducing osteoblastic expression and new bone formation in animal studies. The objective of this study was to evaluate the interactions between the tissue and the bone substitute composed of HA (sintered from bovine bone) in the human body. METHODS: From 2003 to 2005, a total of 33 patients were enrolled to receive the sintered bovine HA as a bone substitute. Inclusion criteria were fractures with bony defects, benign bone tumors with a cavity, and spinal fusions. Bone healing was monitored by a series of radiographs, and bone microstructure was checked by scanning electron microscopy (SEM) and von Kossa staining. RESULTS: In 81.8% (27/33) of cases, significant fusion mass formation was visible in the radiographs after 6-12 months. New bone formation on the surface of the sintered bovine HA was seen under microscopic observation. Tight bonding between the interface of the bone and the sintered bovine HA was shown with SEM/energy-dispersive spectroscopy and von Kossa staining. CONCLUSIONS: Sintered bovine HA is a suitable material as a bone substitute to provide bone growth and promote bone healing.

Chondrogenesis from immortalized human mesenchymal stem cells: comparison between collagen gel and pellet culture methods.

Human mesenchymal stem cells (hMSCs) can differentiate into cells of connective tissue lineages, including cartilage. To overcome the limiting autogenous chondrocyte populations available in cartilage repair, various methods have been developed to maximize chondrogenesis of hMSCs in vitro, most of which use cells derived from primary culture. In this study, we compared chondrogenesis of immortalized hMSCs embedded in collagen gel to those grown in pellet culture. The hMSCs in collagen scaffolds expressed more glycosaminoglycan than those in pellet culture. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that the expression of genes encoding sox-9, aggrecan, and types I and II collagen increased in pellet culture over time. However, in the collagen cultures, only type II collagen and aggrecan expression increased over time, whereas sox-9 expression remained unchanged and type I collagen expression decreased. These results indicate that the immortalized hMSC line is a promising tool for further in vitro chondrogenic studies.

Cytokine release from osteoblasts in response to different intensities of pulsed electromagnetic field stimulation.

We use an in-vitro osteoblast cell culture model to investigate the effects of low-frequency (7.5 Hz) pulsed electromagnetic field (PEMF) stimulation on osteoblast population, cytokines (prostaglandin E(2) (PGE(2)), transforming growth factor beta1(TGFbeta1), and alkaline phosphatase (ALP) activity to find the optimal intensity of PEMF for osteoblast growth. The results demonstrate that PEMF can stimulate osteoblast growth, release of TGFbeta1, and, in addition, an increase of ALP activity. The synthesis and release of PGE(2) in the culture medium are reduced with increasing numbers of cells. Higher intensity does not necessarily mean increased osteoblast growth, and the most efficient intensity is about 2 mV/cm in this case. Although the lower intensities of the PEMF are yet to be determined, the results of this study can shed light on the mechanisms of PEMF stimulation on non union fracture therapy and osteoporosis prevention in the future.

Tissue engineering bone formation in novel recombinant human bone morphogenic protein 2-atelocollagen composite scaffolds.

BACKGROUND: Bone morphogenic proteins (BMPs) are important bone-induction factors, and the development of a suitable carrier for BMPs is a critical step to achieve osteoinductive function. The aims of the present study were to evaluate, at the cellular and molecular levels, the feasibility of recombinant human BMP-2 (rhBMP-2)-collagen composite scaffold and its efficiency for carrying BMP-2 in ectopic bone formation in rats. METHODS: Scaffolds with (test) or without rhBMP-2 (control) were made and implanted into the calf muscle of 16 5-week-old rats. The tissue responses to the scaffolds were examined by histology. Masson's trichrome and von Kossa stainings were performed to examine collagen matrix deposition and calcification at 3, 7, 10, and 14 days. Expressions of bone phenotypic markers, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein were detected by reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS: No detectable adverse responses were noted around the implanted scaffolds, and the area of the resorbed scaffold had been replaced by young connective tissue by 3 to 7 days in both groups. In the rhBMP-2 composite scaffold, collagen matrix deposition was found in the implanted site on day 7 and initial signs of endochondral differentiation also appeared. Mineralization and the expressions of key bone proteins were demonstrated in chondroblasts and osteoblasts at 7 to 14 days. Molecular cascades of bone induction were not shown in control specimens. CONCLUSION: The rhBMP-2-atelocollagen scaffold showed excellent biocompatibility and possessed a bone-inducing capacity in rat within 2 weeks, and, thus, may provide a potential application in tissue engineering of bone tissue.

Preparation and characterization of RGD-immobilized chitosan scaffolds.

Chitosan scaffolds were modified with RGDS (Arg-Gly-Asp-Ser) in the present work via an imide-bond forming reaction between amino groups in chitosan and carboxyl groups in peptides. Successful immobilization was verified with FTIR spectroscopy, and the immobilized amount was determined to be on the order of 10(-12) mol/cm2 through analysis of the immobilized amino acids. Results of experiments of cell culture with rat osteosarcoma (ROS) cells demonstrated that RGDS immobilization could enhance the attachment of ROS cells onto the chitosan, resulting in higher cell density attached to the RGDS-modified scaffold than to the unmodified scaffold. It should be noted that only RGDS, but not other peptide such as RGES, is effective in enhancing cell attachment and possible proliferation. Experiments of in vitro mineralization indicated that there were more cells on the RGDS-modified scaffold than on the unmodified scaffold, which tended to form bone-like tissues. The results presented in this work suggest that immobilization of RGDS can make chitosan scaffolds more compatible for the culture of osteoblast-like cells and the regeneration of bone-like tissues.

Lineage differentiation-associated loss of adenoviral susceptibility and Coxsackie-adenovirus receptor expression in human mesenchymal stem cells.

Previous reports debated the effects of differentiation on adenoviral vector (AdV) transduction efficiency and Coxsackie-adenovirus receptor (CAR) expression. This prompted us to investigate the efficiency of AdV transduction and CAR expression in human mesenchymal stem cells (hMSCs) and their differentiated progeny. Current results revealed high efficiency (>90%) of AdV transduction and a consistent level of CAR expression in hMSCs by the use of AdV carrying the enhanced green fluorescent protein reporter gene. Competition of CAR with blocking monoclonal antibody RmcB resulted in a reduction in transduction efficiency, indicating the CAR involvement in transduction of hMSCs. The cells were then induced to differentiate into bone, fat, or neural cells, and results demonstrated that the differentiation was accompanied with a consistent decline in AdV transduction and a decrement in CAR expression. Cells were infected with AdV and then induced into differentiation, and results demonstrated that transduced cells preserved differentiation potentials and still had transgene expression in a subpopulation of cells for 4 weeks and even in tested lineage-specific differentiation. According to the present investigation, undifferentiated hMSCs can serve as a gene-delivering system, and gene transfer into hMSCs before differentiation can resolve the difficulties in transduction of their differentiated progeny.

Correlation of MR lumbar spine bone marrow perfusion with bone mineral density in female subjects.

PURPOSE: To prospectively assess lumbar spine bone marrow perfusion at dynamic magnetic resonance (MR) imaging and correlate perfusion with bone mineral density (BMD) in female subjects. MATERIALS AND METHODS: BMD measurement and dynamic MR imaging of the lumbar spine were performed in 69 female subjects (mean age +/- standard deviation, 57 years +/- 11). Subjects were stratified into premenopausal (n = 19) and postmenopausal (n = 50) groups, with the latter group including both women who were (n = 13) and women who were not (n = 37) receiving hormone replacement therapy. BMD (in grams per square centimeter) was measured with dual energy absorptiometry in the lumbar spine. Peak enhancement ratio, measured with time-signal intensity curves calculated from dynamic MR image data, represented bone marrow perfusion. Peak enhancement ratio was compared with age and BMD by using linear regression analysis and Pearson correlation. RESULTS: A significant positive correlation was found for BMD with peak enhancement ratio of lumbar vertebrae among all subjects (n = 69, r = 0.63, P <.001), all postmenopausal women (n = 50, r = 0.50, P <.001), and postmenopausal women without hormone replacement therapy (n = 37, r = 0.61, P <.001). However, the correlation between BMD and peak enhancement ratio was not significant (P >.05) in premenopausal women (n = 19) or postmenopausal women receiving hormone therapy (n = 13). Both BMD and peak enhancement ratio were inversely correlated with age (P <.001, Pearson correlation). Pearson partial correlation coefficient for peak enhancement ratio and mean in all subjects, with control for inverse correlation with age, was significant (r = 0.63, P <.001). CONCLUSION: Significant correlation was found between the peak enhancement ratio of vertebral bone marrow and BMD in postmenopausal female subjects. This result may suggest a vascular component in the pathogenesis of osteoporosis.