BackgroundAdipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP.MethodsWe performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 107 cells/disc (n = 5) or 4 × 107 cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year.ResultsNo patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI.ConclusionsCombined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population.Trial registrationClinicalTrials.gov NCT02338271. Registered 7 January 2015.

A root attachment injury (root tear) of the meniscus can abolish the ability of the meniscus to bear hoop stress and predispose to increase articular contact stress which contribute to femorotibial degenerative changes. A pull out suture technique to repair the root tear has been described, but the procedure making the tibial tunnel may be difficult and troublesome. This article describes a repair technique using a suture anchor and posterior trans-septal portal.

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Purpose:We wanted to investigate the grip and pinch strength of hands and establish the clinical normative data for Korean people. Materials and Methods: A sample of 234 Korean males and 281 Korean females (age: 10 to 84) were tested. Grip strength and pinch strength were tested twice with 5 minute interval between tests. Results: Generally, hand strength peaked at 30 to 39 of age for both males and females. The average grip strength was 48.8 kg for males and 28.23 kg for females and they were 11% stronger than 12 years before in both groups. Tip pinch strength peaked in the forties, but key pinch and tripod pinch peaked in the thirties. All the peak hand strength was obtained in the 30 to 39 age group of females. Among the pinch strengths, key pinch was the strongest. For the right-handed people, the grip and pinch strengths of the right hand were stronger than those of the left hand. However, for the left-handed people, the left hand was stronger than the right hand only for the tripod pinch (p＜0.005). Conclusion:The hand strength of Koreans peaked in the 30 to 39 age group. Key pinch was the strongest among the three pinch strengths. Right-handed people have a stronger right hand than the left hand, but the left-handed people have almost the same hand strength in both hands, except for the tripod pinch.

Genetic factors have been shown to be a small but significant predictor for osteoporosis and osteoporotic fracture risk. We performed a case-control association study to determine the association between miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms and osteoporotic vertebral compression fracture (OVCF) susceptibility. In total, 286 unrelated postmenopausal Korean women (57 with OVCFs, 55 with non-OVCFs, and 174 healthy controls) were recruited. All subjects underwent dual energy X-ray absorptiometry to determine BMD at the lumbar spine and femoral neck. We focused on four single nucleotide polymorphisms (SNPs) of pre-miRNA sequences including miR-146aC>G (rs2910164), miR-149T>C (rs2292832), miR-196a2T>C (rs11614913), and miR-499A>G (rs3746444). Genotype frequencies of these four SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. The TT genotype of miR-149aT>C was less frequent in subjects with OVCFs, suggesting a protective effect against OVCF risk (Odds ratio [OR], 0.435; 95% confidence interval [CI], 0.22-0.85, p = 0.014), whereas the miR-146aCG/ miR-196a2TC combined genotype was more frequent in OVCF patients (OR, 5.163; 95%CI, 1.057-25.21, p = 0.043), suggesting an increase in OVCF risk. Additionally, combinations of miR-146a, -149, -196a2, and -449 showed a significant association with increased prevalence of OVCFs in postmenopausal women. In particular, the miR-146aG/-149T/-196a2C/-449G allele combination was significantly associated with an increased risk of OVCF (OR, 35.01; 95% CI, 1.919-638.6, p = 0.001). Our findings suggest that the TT genotype of miR-149aT>C may contribute to decreased susceptibility to OVCF in Korean postmenopausal women. Conversely, the miR-146aCG/ miR-196a2TC combined genotype and the miR-146aG/-149T/-196a2C/-449G allele combination may contribute to increased susceptibility to OVCF. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:244-253, 2018.

Osteoporotic vertebral compression fractures (OVCFs) are serious health problems. We conducted a randomized, open-label, phase I/IIa study to determine the feasibility, safety, and effectiveness of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) and teriparatide (parathyroid hormone 1-34) in OVCFs. Twenty subjects with recent OVCFs were randomized to teriparatide (20 μg/day, daily subcutaneous injection for 6 months) treatment alone or combined treatment of WJ-MSCs (intramedullary [4 × 10 7 cells] injection and intravenous [2 × 10 8 cells] injection after 1 week) and teriparatide (20 μg/day, daily subcutaneous injection for 6 months). Fourteen subjects (teriparatide alone, n = 7; combined treatment, n = 7) completed follow-up assessment (visual analog scale [VAS], Oswestry Disability Index [ODI], Short Form-36 [SF-36], bone mineral density [BMD], bone turnover measured by osteocalcin and C-terminal telopeptide of type 1 collagen, dual-energy x-ray absorptiometry [DXA], computed tomography [CT]). Our results show that (a) combined treatment with WJ-MSCs and teriparatide is feasible and tolerable for the patients with OVCFs; (b) the mean VAS, ODI, and SF-36 scores significantly improved in the combined treatment group; (c) the level of bone turnover markers were not significantly different between the two groups; (d) BMD T-scores of spine and hip by DXA increased in both control and experimental groups without a statistical difference; and (e) baseline spine CT images and follow-up CT images at 6 and 12 months showed better microarchitecture in the combined treatment group. Our results indicate that combined treatment of WJ-MSCs and teriparatide is feasible and tolerable and has a clinical benefit for fracture healing by promoting bone architecture. Clinical trial registration: https://nedrug.mfds.go.kr/, MFDS: 201600282-30937.

It was reported that substance P had beneficial effects in the healing of acute tendon injury. However, the relationship between substance P and degenerative tendinopathy development remains unclear. The purpose of this study was to determine the role of substance P in the pathogenesis of tendinopathy. Healthy and tendinopathy tendon were harvested from human and tenocytes were cultured individually. The expression levels of genes associated with tendinopathy were compared. Next, substance P was exogenously administered to the healthy tenocyte and the effect was evaluated. The results showed that tendinopathy tenocytes had higher levels of COL3A1, MMP1, COX2, SCX, ACTA2, and substance P gene expression compared to healthy tenocytes. Next, substance P treatment on the healthy tenocyte displayed similar changes to that of the tendinopathy tenocytes. These differences between the two groups were also determined by Western blot. Additionally, cells with substance P had the tendinopathy change morphologically although cellular proliferation was significantly higher compared to that of the control group. In conclusion, substance P enhanced cellular proliferation, but concomitantly increased immature collagen (type 3 collagen). Substance P plays a crucial role in tendinopathy development and could be a future therapeutic target for treatment.