Abstract Background The reconstruction of tendons with large defects requires grafts with high mechanical strength and is often hindered by complications such as infection and adhesion. Hence, grafts combining the advantages of mechanical resilience and antibacterial/antiadhesion activity are highly sought after. Methods The silver nanoparticles (GA-Ag NPs) synthesized from gallic acid and silver nitrate were attached to a decellularized extracellular matrix (Decellularized Tendon crosslinking GA-AgNPs, DT-Ag). We examined the histological structure, mechanical property, morphology, Zeta potential, cytotoxicity, antibacterial properties, antioxidant and anti-inflammatory properties, and ability of the DT-Ag to treat tendon defects in animals. Results Approximately 108.57 ± 0.94 μg GA-Ag NPs loaded per 50 mg DT, the cross-linked part of GA-Ag NPs was 65.47 ± 0.57%, which provided DT-Ag with long-lasting antibacterial activity. Meanwhile, GA endowed DT-Ag with good antioxidant and anti-inflammatory activities. Additionally, The DT-Ag facilitated M2 macrophage polarization, and suppressed fibrin deposition by hindering fibroblast adhesion. Mormore, the main advantages of DT-Ag, namely its long-lasting antibacterial activity (tested using Escherichia coli and Staphylococcus aureus as models) and the ability to prevent tissue adhesion were confirmed in vivo. Conclusion The fabricated multifunctional tendon graft was highly hydrophilic, biocompatible, and mechanically resilient, and concluded to be well suited for dealing with the main complications of surgical tendon reconstruction and has bright application prospects. Graphical Abstract

Bone marrow adipose tissue has brown fat characteristics. Several studies have demonstrated that total flavonoids of Epimedium (TFE) could prevent bone loss and reduce the white adiposity in bone marrow induced by ovariectomy (OVX) in rats. However, the effects of TFE on marrow brown fat in OVX rats remain unclear. In this word, we addressed this question expected to provide a new target for preventing and treating osteoporosis. Thirty-six 3-month-old female Sprague-Dawley rats were equally divided into Sham controls, OVX controls, and OVX treated with TFE. Chemical shift coding magnetic resonance was performed to detect marrow fat fraction at the left femur at baseline, 6 and 12 weeks post-OVX. Bone mineral density at the lumbar spine and femur was measured by dual-energy x-ray absorptiometry. Serum bone biomarkers by ELISA, trabecular bone microarchitecture at the proximal tibia by micro-CT, quantitative parameters of marrow adipocyte by hematoxylin, and eosin staining were evaluated. The marrow adipocyte gene and protein expressions profile were determined by real-time quantitative PCR and immunostaining in whole tibiae. We found that TFE treatment could decrease bone turnover rate and improved bone mineral density and trabecular microarchitecture in OVX rats. OVX resulted in marrow adipogenesis as evidenced by increased marrow fat fraction, larger marrow adipocyte size, increased adipocyte number and percentage of adipocyte area, marrow white adipocyte gene, and protein expression, including PPARγ2 and FABP4. These pathological changes induced by estrogen deficiency were restored by TFE treatment. TFE also increased brown adipocyte expressions of the transcription factor Ucp1 and Prdm16 in whole tibiae. There was no detectible protein expression of brown adipocyte markers in the proximal tibia. Taken together, TFE regulation of bone marrow adiposity in OVX rats is mediated, at least in part, via maintaining the reciprocity of white and brown adipose tissue.

Abstract Objective The aim of the study was to determine whether serum iron and ferritin levels are determinants of iron accumulation in bone marrow using a three-dimension Fat Analysis & Calculation Technique (FACT) sequence. Methods We measured spinal marrow R2* using a 3T FACT sequence in 112 postmenopausal women (mean age, 62.6 years; range, 50–82.6 years). Serum iron and ferritin levels were determined in blood specimens. Lumbar spine bone mineral density was measured by dual-energy x-ray absorptiometry. The levels of serum iron and ferritin were evaluated in relation to the spinal marrow R2* values before and after adjustments for potential confounders. Results In the unadjusted model, magnetic resonance imaging–based spinal marrow R2* was positively correlated to the levels of serum ferritin (Spearman ρ = 0.436, P < 0.001) and iron (Spearman ρ = 0.245, P = 0.009). Multiple stepwise linear regression analyses (adjusting for age, years since menopause, body mass index, alcohol intake, tobacco use, physical activity, serum lipids profile, biomarkers of bone turnover, and lumbar spine bone density) were performed in 3 separate models with marrow R2* values as potential explanatory variables. The level of serum ferritin, but not iron, was an independent predictor of marrow R2* (standardized β coefficient, 0.302, 95% confidence interval, 0.141–0.509, P = 0.001). Similarly, spinal marrow R2* increased with a linear trend from the lowest (<139 ng/mL) to highest (≥180 ng/mL) serum ferritin quartiles (P for trend = 0.007). Conclusions Quantitative assessment of R2* derived from FACT is a fast, simple, noninvasive, and nonionizing method to evaluate marrow iron accumulation.

OBJECTIVE:To assess the differential features of marrow adiposity between osteoarthritis (OA) and osteoporosis (OP) in postmenopausal women using water/fat MRI. METHODS:This cross-sectional study included 97 postmenopausal women (OA [n = 25], OA + osteopenia [n = 27], OA + OP [n = 23], and OP groups [n = 22]). Water/fat MRI, dual-energy x-ray absorptiometry and biochemical analysis were performed to assess vertebral marrow fat fraction, bone mineral density, and bone biomarkers, respectively. Harris Hip Score was recorded to evaluate hip function. RESULTS:There were significant differences in marrow fat content among the OA, OA + osteopenia, and OA + OP groups, between OP and OA participants with normal bone mass or osteopenia (all P < 0.05); no significant difference was observed between OA + OP and OP groups. Serum levels of leptin and β-Crosslaps in OA with normal bone mass and osteopenic OA groups were higher than in OP group. Marrow fat fraction was inversely correlated with Harris Hip Score (r = -0.371, P = 0.013), bone mineral density (r = -0.554, P = 0.009) and leptin levels (r = -0.610, P < 0.001). In multivariate regression analysis, marrow fat fraction was found to have a consistent and unchanged inverse association with leptin levels (Sβ = -0.311, P = 0.002) and bone mineral density (Sβ =  -0.265, P = 0.006) after adjusting for age, years since menopause, and body mass index. CONCLUSIONS:Postmenopausal OA with OP have a phenotype with higher marrow adiposity. OA and OP could coexist, for the presence of a specific subgroup of OA with increased marrow fat accumulation and high risk of developing OP.

PURPOSE:To validate a chemical shift-encoded (CSE) water-fat imaging for quantifying marrow fat fraction (FF), using proton magnetic resonance spectroscopy (MRS) as reference.MATERIALS AND METHODS:Multiecho T2 -corrected MRS and CSE imaging with eight-echo gradient-echo acquisitions at 3T were performed to calculate marrow FF in 83 subjects, including 41 with normal bone mineral density (BMD), 26 with osteopenia, and 16 with osteoporosis (based on DXA). Eight participants were scanned three times with repositioning to assess the repeatability of CSE FF map measurements. Pearson correlation coefficient, Bland-Altman 95% limit of agreement, and Lin's concordance correlation coefficient were calculated.RESULTS:The Pearson correlation coefficient was 0.979 and Lin's concordance correlation coefficient was 0.962 between CSE-based FF and MRS-based FF. All data points, calculated using the Bland-Altman method, were within the limits of agreement. The intra- and interrater agreement for average CSE-based FF was excellent (intrarater, intraclass correlation coefficient [ICC] = 0.993; interrater, ICC = 0.976-0.982 for different BMD groups). In the subgroups of varying BMD, inverse correlations were observed to be very similar between BMD (r = -0.560 to -0.710), T-score (r = -0.526 to -0.747), and CSE-based FF, and between BMD (r = -0.539 to -0.706), T-score (r = -0.501 to -0.742), and MRS-based FF even controlling for age, years since menopause, and body mass index. The repeatability for CSE FF map measurements expressed as absolute precision error was 1.45%.CONCLUSION:CSE imaging is equally accurate in characterizing marrow fat content as MRS. Given its excellent correlation and concordance with MRS, the CSE sequence could be used as a potential replacement technique for marrow fat quantification.LEVEL OF EVIDENCE:1 J. Magn. Reson. Imaging 2017;45:66-73.

Bisphenol A diglycidyl ether (BADGE), a PPARγ2 antagonist, has been shown to inhibit marrow adipogenesis and promote bone formation in intact animals. We investigated the impact of BADGE on a new and more clinically relevant physiological model, the ovariectomized (OVX) rat model. Forty female Wistar rats were divided into four treatment groups for 12 wk ( n = 10/group): sham+vehicle, sham+BADGE, OVX+vehicle, and OVX+BADGE. Postmortem analyses included MRI, micro-CT, serological test, histomorphometry, biomechanical tests, RT-PCR, and Western blot. Overall, OVX induced a sequential marrow fat expansion accompanied by bone deterioration. Compared with OVX controls, BADGE reduced fat fraction of the distal femur by 36.3%, adipocyte density by 33.0%, adipocyte size by 28.6%, adipocyte volume percentage by 57.8%, and adipogenic markers PPARγ2 and C/EBPα by ∼50% in OVX rats. Similar results were observed in sham rats vs. vehicle. BADGE could promote bone quality in sham rats; however, BADGE did not significantly improve trabecular microarchitecture, biomechanical strength, and dynamic histomorphometric parameters except for trabecular separation in OVX rats. We concluded that early BADGE treatment at a dose of 30 mg/kg attenuates marrow adiposity in ovary-intact and OVX rats and stimulates bone formation in ovary-intact rats but does not significantly rescue bone quality in OVX rats.

We tested the short- and midterm reproducibility of vertebral marrow fat fraction (FF) measurements using mDixon imaging.