Meclozine ameliorates skeletal muscle pathology and increases muscle forces in mdx mice.

We screened pre-approved drugs for the survival of the Hu5/KD3 human myogenic progenitors. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, promoted the proliferation and survival of Hu5/KD3 cells. Meclozine increased expression of MyoD, but reduced expression of myosin heavy chain and suppressed myotube formation. Withdrawal of meclozine, however, resumed the ability of Hu5/KD3 cells to differentiate into myotubes. We examined the effects of meclozine on mdx mouse carrying a nonsense mutation in the dystrophin gene and modeling for Duchenne muscular dystrophy. Intragastric administration of meclozine in mdx mouse increased the body weight, the muscle mass in the lower limbs, the cross-sectional area of the paravertebral muscle, and improved exercise performances. Previous reports show that inhibition of phosphorylation of ERK1/2 improves muscle functions in mouse models for Emery-Dreifuss muscular dystrophy and cancer cachexia, as well as in mdx mice. We and others previously showed that meclozine blocks the phosphorylation of ERK1/2 in cultured cells. We currently showed that meclozine decreased phosphorylation of ERK1/2 in muscles in mdx mice but not in wild-type mice. This was likely to be one of the underlying mechanisms of the effects of meclozine on mdx mice.

Biceps tenotomy versus soft-tissue tenodesis in females aged 60 years and older with rotator cuff tears.

BACKGROUND: Recently, to treat the long head of the biceps tendon lesions in addition to rotator cuff repair has been recommended. However, the differences in clinical outcomes between biceps tenotomy and tenodesis for middle-aged and elderly females remains unclear. The purpose of this study was to compare the outcomes of biceps tenotomy and soft-tissue tenodesis that were performed concurrently with arthroscopic rotator cuff repair in ≥60-year-old females. METHODS: Female shoulders that underwent arthroscopic rotator cuff repair in our institute in 2016 were retrospectively reviewed. This study included 66 shoulders with concurrent biceps tenotomy or soft-tissue tenodesis: tenotomy group, 41 shoulders; soft-tissue tenodesis group, 25 shoulders. Clinical scores, biceps pain (visual analogue scale, VAS), Popeye deformity, and biceps strength (%contralateral side) were compared between the two groups. RESULTS: The mean age was significantly higher in the tenotomy group than the soft-tissue tenodesis group (72 ± 4 and 68 ± 6 years, respectively; P = 0.002). There were no significant differences in post-operative JOA and UCLA scores between the groups. VAS for biceps pain was significantly higher at postoperative 6 months in the tenotomy group than the soft-tissue tenodesis group (2.9 ± 2.5 and 1.7 ± 1.6, respectively, P = 0.03), though there were no significant differences at postoperative 3, 12, and ≥24 months. Subjective evaluation of Popeye deformity was not significantly different between the groups. Postoperative biceps strength was significantly lower in the tenotomy group than the soft-tissue tenodesis group (89.9% and 102.8%, respectively, P = 0.02). CONCLUSIONS: Both biceps tenotomy and soft-tissue tenodesis concurrent with rotator cuff repair in ≥60-year-old female patients resulted in good outcomes. Shoulders with soft-tissue tenodesis demonstrated earlier improvement in postoperative biceps pain and better postoperative biceps strength than those with tenotomy. There were no differences in objective and subjective Popeye deformity between tenotomy and soft-tissue tenodesis. The LHB procedures, tenotomy or tenodesis, can be selected depending on surgeons' preference.

Evaluation of muscle quality and quantity for the assessment of sarcopenia using mid-thigh computed tomography: a cohort study.

BACKGROUND: For the diagnosis of Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP) revised the algorisms in 2019, where they added computed tomography (CT) as an assessment tool not only for quantity but also for quality in research purpose. However, the evidence for clinical appreciation of CT has been lacking. Therefore, we investigated the correlation between CT and various motor function tests to assess the utility of CT as a potential diagnostic tool for sarcopenia. METHODS: In total, 214 patients who were examined at our center during the study period (2016-2017) were included in the study. Single-slice CT scan of the mid-thigh region was performed, from which cross-sectional area (CSA) and CT attenuation value (CTV) of quadriceps femoris were evaluated for each subject. Other assessments included skeletal muscle mass index by DXA and BIA, muscle strength and physical performance. Furthermore, subjects were classified into four groups as per the Asia Working Group of Sarcopenia (AWGS) 2019 criteria as those with: normal, poor muscle function/strength (poor function), sarcopenia and severe sarcopenia. RESULTS: Knee muscle strength correlated with CSA (r = 0.60) and the correlation was significantly greater than that with DXA and BIA. For physical performance, standing-up test correlated with CSA (r = - 0.20) and CTV (r = - 0.40) and walking speed with CTV (r = 0.43), which was significantly greater than that with DXA and BIA. The CSA was significantly lower in women with sarcopenia group and in both men and women with severe sarcopenia (all p < 0.01). Furthermore, CTV was significantly lower in women with poor-function and in both men and women with severe sarcopenia group (all p < 0.01). CONCLUSIONS: CSA mostly correlated with muscle strength, whereas CTV mostly correlated with physical performance. CT with measurements of CSA and CTV enables the evaluation of muscle mass and quality simultaneously. CT is believed to be useful in inferring evaluation of motor function and assessment of sarcopenia.

Delayed anterior cruciate ligament reconstruction increases the incidence of medial meniscal bucket handle tears and medial compartment chondral injuries in patients aged 40 years and older.

INTRODUCTION: No widely accepted evidence-based indications exist for the initial surgical management of patients with anterior cruciate ligament (ACL) injuries ≥ 40 years old, and treatment for these patients remains controversial. This study aimed to evaluate the association between elapsed time from ACL injury to surgery and the incidence of meniscal tears and chondral injury in patients aged ≥ 40 years. MATERIALS AND METHODS: The patients who underwent primary ACL reconstruction were divided into two groups based on elapsed time from injury to surgery: early group, < 12 months; and delayed group, ≥ 12 months. Patient records were reviewed for incidence and types of meniscal tears and chondral injuries in each group. Chondral injury grades were evaluated with International Cartilage Regeneration and Joint Preservation Society (ICRS) Criteria. RESULTS: This study evaluated 67 knees in the early group and 33 knees in the delayed group. Mean ages in each group were 46.9 ± 6.5 and 46.9 ± 6.0. The delayed group showed significantly higher rates of medial meniscal tear [31 of 33, 93.9% vs 29 of 67, 43.3%; P < 0.0001; odds ratio (OR), 20.31; 95% confidence interval (CI), 4.49-91.9], medial femoral condyle chondral injuries ≥ ICRS grade II (15 of 33, 45.5% vs 8 of 67, 11.9%; P < 0.001; OR, 6.15; 95% CI 2.24-16.83), and medial tibial chondral injuries ≥ ICRS grade II (7 of 33, 21.2% vs 3 of 67, 4.5%; P < 0.05; OR, 5.74; 95% CI 1.38-23.9) compared with the early group. With respect to types of medial meniscal tear, the delayed group showed a significantly higher frequency of bucket handle tears (11 of 33, 33.3%) compared with the early group (2 of 67, 3.0%; P < 0.0001; OR, 16.25; 95% CI 3.34-79.1). CONCLUSIONS: Delayed ACL reconstruction was associated with increased incidence of chondral injuries and medial meniscal tears, particularly bucket handle tears in this cohort. LEVEL OF EVIDENCE: Level III.

Spontaneous Pneumomediastinum in an Adolescent Soccer Player.

Spontaneous pneumomediastinum (SPM) is an uncommon and usually benign self-limiting clinical disorder found in young people, often without apparent precipitating factors or diseases. A pressure gradient exists between the peripheral pulmonary alveoli and the hilum, and increased intra-alveolar pressure causes rupture of the terminal alveoli. We present the case of a 15-year-old male soccer player who presented with a complaint of anterior chest pain and dysphagia after stopping the strong ball with his chest. His symptom gradually progressed over hours. We can make the diagnosis of SPM using by chest X-ray and computed tomography (CT) scanning. His symptoms were gradually resolved over the course of approximately one week with no exercise and careful observation. We believe that our case provides very useful information to alert clinicians and coaches regarding this rare disease that may occur in anyone including adolescent soccer players.

Osteoarthritis-derived chondrocytes are a potential source of multipotent progenitor cells for cartilage tissue engineering.

The natural healing capacity of damaged articular cartilage is poor, rendering joint surface injuries a prime target for regenerative medicine. While autologous chondrocyte or mesenchymal stem cell (MSC) implantation can be applied to repair cartilage defects in young patients, no appropriate long-lasting treatment alternative is available for elderly patients with osteoarthritis (OA). Multipotent progenitor cells are reported to present in adult human articular cartilage, with a preponderance in OA cartilage. These facts led us to hypothesize the possible use of osteoarthritis-derived chondrocytes as a cell source for cartilage tissue engineering. We therefore analyzed chondrocyte- and stem cell-related markers, cell growth rate, and multipotency in OA chondrocytes (OACs) and bone marrow-derived MSCs, along with normal articular chondrocytes (ACs) as a control. OACs demonstrated similar phenotype and proliferation rate to MSCs. Furthermore, OACs exhibited multilineage differentiation ability with a greater chondrogenic differentiation ability than MSCs, which was equivalent to ACs. We conclude that chondrogenic capacity is not significantly affected by OA, and OACs could be a potential source of multipotent progenitor cells for cartilage tissue engineering.

Hypoxia-inducible factor-2α induces expression of type X collagen and matrix metalloproteinases 13 in osteoarthritic meniscal cells.

OBJECTIVES: To evaluate whether Hypoxia-inducible factor-2α (HIF-2α) regulates expression of endochondral ossification-related molecules in human OA meniscus. METHODS: Expressions of HIF-2α, type X collagen (COL10), matrix metalloproteinase (MMP)-13, and vascular endothelial growth factor (VEGF) in non-OA and OA menisci were analyzed by real-time RT-PCR and immunohistochemistry (IHC). Meniscal cells from OA patients were treated with interleukin-1ß (IL-1ß) and gene expression was analyzed. After knockdown of HIF-2α in OA meniscal cells, COL10 and MMP-13 expression were analyzed by RT-PCR, western blotting, immunofluorescence and ELISA. RESULT: Histological analysis demonstrated weak staining of the superficial layer and large round cells in OA meniscus. RT-PCR analysis showed that HIF-2α, COL10, MMP-13, and VEGF mRNA expressions were higher in OA than non-OA meniscal cells. IHC showed a coordinated staining pattern of HIF-2α, COL10, and MMP-13 in OA meniscus. IL-1ß treatment increased HIF-2α, COL10, and MMP-13 expressions in OA meniscal cells, and knockdown of HIF-2α suppressed IL-1ß-mediated increase in COL10 and MMP-13 expression. CONCLUSIONS: These results suggested that HIF-2α may cause meniscal matrix degradation by transactivation of MMP-13. HIF-2α may be a therapeutic target for modulating matrix degradation in both articular cartilage and meniscus during knee OA progression.

Does the Q - H index show a stronger relationship than the H:Q ratio in regard to knee pain during daily activities in patients with knee osteoarthritis?

[Purpose] The purpose of this study was to elucidate the relationship between knee muscle strength and knee pain in activities of daily living, based on consideration of the difference between extension and flexion strength (Q - H) and the hamstring:quadriceps (H:Q) ratio in patients with knee osteoarthritis. [Subjects and Methods] The participants were 78 females with knee osteoarthritis, and a total of 133 knees that had not been treated surgically were the targets of this research. The legs were divided according to dominance. Isometric knee extension and flexion muscle strength and knee pain during activities of daily living were measured. The H:Q ratio (flexion/extension muscle strength) and the difference between extension and flexion strength, (extension muscle strength/weight) minus (flexion muscle strength/weight), that is, Q - H, were calculated. The correlation between these indices and the knee pain score during activities of daily living was investigated. [Results] Greater knee pain during activities of daily living was related to lower knee extension muscle strength and Q - H in both the dominant and nondominant legs. Knee flexion muscle strength and the H:Q ratio were not significantly correlated with knee pain during any activities of daily living. [Conclusion] Knee extension muscle strength and Q - H were found to be significantly correlated with knee pain during activities of daily living, whereas the H:Q ratio was not.

Expression of tenocyte lineage-related factors in regenerated tissue at sites of tendon defect.

BACKGROUND: The healing mechanism of ruptured or injured tendons is poorly understood. To date, some lineage-specific factors, such as scleraxis and tenomodulin, have been reported as markers of tenocyte differentiation. Because few studies have focused on tenocyte lineage-related factors with respect to the repaired tissue of healing tendons, the aim of this study was to investigate their expression during the tendon healing process. METHODS: Defects were created in the patellar tendons of rats, and the patellae and patellar tendons were harvested at 3 days and at 1, 2, 3, 6, 12, and 20 weeks after surgery. They were studied using micro-computed tomography, and paraffin-embedded sections were then prepared for histological evaluation. Reverse transcription-polymerase chain reactions were performed to analyze the expression of genes related to the tenocyte lineage, chondrogenesis, and ossification. RESULTS: Repaired tissue became increasingly fibrous over time and contained a greater number of vessels than normal tendons, even in the later period. Safranin O staining revealed the existence of proteoglycan at 1 week and its persistence through 20 weeks. Ossification was detected in all tendons at 12 weeks. The expression of tenocyte lineage-related genes was high at 1 and 2 weeks. Chondrogenic genes were up-regulated until 6 weeks. Runt-related transcription factor 2, an osteogenic gene, was up-regulated at 20 weeks. CONCLUSIONS: In our tendon defect model, cells participating in the tendon healing process appeared to differentiate toward tenocyte lineage only in the early phase, and chondrogenesis seemed to occur from the early phase onward. To improve tendon repair, it will be necessary to promote and maintain tenogenesis and to inhibit chondrogenesis, especially in the early phase, in order to avoid erroneous differentiation of stem cells.

＜Editors' Choice＞ The relationship between preoperative foot alignment and postoperative outcomes in patients who underwent initial total knee arthroplasty.

We compared the relationship between foot alignments and quality of life in patients who underwent initial total knee arthroplasty (TKA). Among the patients with knee osteoarthritis (KOA) who underwent TKA from May 2015 to May 2017 at our hospital, we focused on those in whom weight-bearing foot radiographs had been evaluated preoperatively. The hallux valgus angle and Meary angle were measured by preoperative radiography, and those with hallux valgus angles of 20 degrees or more were classified into the hallux valgus (HV) group, and those with Meary angles of 4 degrees or more into the high arch (HA) group. Also knee and ankle range of motion, knee pain Visual Analog Scale, and the 36-item short-form health survey (SF-36) were measured preoperatively and at discharge, and the amount of these changes was compared in the presence/absence of HV and HA. Regarding HV, there were no significant differences in any of these items between the HV and non-HV groups. However, the SF-physical function was significantly lower in the HA group than in the normal group. In addition, ankle dorsiflexion was lower in the HA group than that in the normal group, although this difference was not statistically significant. There was little improvement of the ankle dorsiflexion, and it was associated with deterioration of the physical function items of SF-36. In total knee arthroplasty patients with HA, physical therapy of the ankles and feet, as well as of the knees, was considered to enhance the improvement of physical function.

Chondrogenic capacity and alterations in hyaluronan synthesis of cultured human osteoarthritic chondrocytes.

During osteoarthritis there is a disruption and loss of the extracellular matrix of joint cartilage, composed primarily of type II collagen, aggrecan and hyaluronan. In young patients, autologous chondrocyte implantation can be used to repair cartilage defects. However, for more elderly patients with osteoarthritis, such a repair approach is contraindicated because the procedure requires a large expansion of autologous chondrocytes in vitro leading a rapid, perhaps irreversible, loss of the chondrocyte phenotype. This study investigates whether osteoarthritic chondrocytes obtained from older patients can be expanded in vitro and moreover, induced to re-activate their chondrocyte phenotype. A decrease in chondrocyte phenotype markers, collagen II, aggrecan and SOX9 mRNA was observed with successive expansion of cells in monolayer culture. However, chondrogenic induction in three-dimensional pellet culture successfully rescued the expression of all three marker genes to native levels, even with 4th passage cells-cells representing an approximate 625-fold expansion in cell number. This data supports the use of osteoarthritic cells for autologous implantation repair. In addition, another set of gene products were explored as useful markers of the chondrocyte phenotype. Differentiated primary chondrocytes exhibited a common pattern of hyaluronan synthase isoforms that changed upon cell expansion in vitro and, reverted back to the original pattern following pellet culture. Moreover, the change in isoform pattern correlated with changes in the molecular size of synthesized hyaluronan.

Surface markers and gene expression to characterize the differentiation of monolayer expanded human articular chondrocytes.

Autologous chondrocyte implantation (ACI) is a method of cartilage repair. To improve the quality of regenerated tissue by ACI, it is essential to identify surface marker expression correlated with the differentiation status of monolayer expanded human articular chondrocytes and to define the index for discriminating dedifferentiated cells from monolayer expanded human articular chondrocytes. Normal human articular chondrocytes were cultured in monolayer until passage 4. At each passage, mRNA expression of collagen type I, II, and X and aggrecan was analyzed by real-time quantitative PCR, and the surface marker expression of CD14, CD26, CD44, CD49a, CD49c, CD54, and CD151 was analyzed by fluorescence-activated cell sorting (FACS). The ratios of mRNA levels of collagen type II to I (Col II/Col I) represented the differentiation status of chondrocytes more appropriately during monolayer culture. The surface marker expression of CD44, CD49c, and CD151 was upregulated according to the dedifferentiation status, whereas that of CD14, CD49a, and CD54 was downregulated. The most appropriate combination of the ratio of Col II/Col I was CD54 and CD44. Cell sorting was performed using a magnetic cell sorting system (MACS) according to CD54 and CD44, and real-time quantitative PCR was performed for the cell subpopulations before and after cell sorting. The expression of collagen type II and aggrecan of the chondrocytes after MACS was higher than that before sorting, but not significantly. The mean fluorescence intensity (MFI) ratio of CD54 to CD44 could be an adequate candidate as the index of the differentiation status.

Role of S100A12 in the pathogenesis of osteoarthritis.

S100A12 is a member of the S100 protein family, which are intracellular calcium-binding proteins. Although there are many reports on the involvement of S100A12 in inflammatory diseases, its presence in osteoarthritic cartilage has not been reported. The purpose of this study was to investigate the expression of S100A12 in human articular cartilage in osteoarthritis (OA) and to evaluate the role of S100A12 in human OA chondrocytes. We analyzed S100A12 expression by immunohistochemical staining of cartilage samples obtained from OA and non-OA patients. In addition, chondrocytes were isolated from knee cartilage of OA patients and treated with recombinant human S100A12. Real-time RT-PCR was performed to analyze mRNA expression. Protein production of matrix metalloproteinase 13 (MMP-13) and vascular endothelial growth factor (VEGF) in the culture medium were measured by ELISA. Immunohistochemical analyses revealed that S100A12 expression was markedly increased in OA cartilages. Protein production and mRNA expression of MMP-13 and VEGF in cultured OA chondrocytes were significantly increased by treatment with exogenous S100A12. These increases in mRNA expression and protein production were suppressed by administration of soluble receptor for advanced glycation end products (RAGE). Both p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) inhibitors also suppressed the increases in mRNA expression and protein production of MMP-13 and VEGF. We demonstrated marked up-regulation of S100A12 expression in human OA cartilages. Exogenous S100A12 increased the production of MMP-13 and VEGF in human OA chondrocytes. Our data indicate the possible involvement of S100A12 in the development of OA by up-regulating MMP-13 and VEGF via p38 MAPK and NF-κB pathways.

Outcomes of pediatric anterior cruciate ligament reconstructions in patients with and without bucket handle meniscus repairs.

The purpose of this study was to report the outcomes of concomitant bucket handle meniscal tear (BHMT) repair and anterior cruciate ligament (ACL) reconstruction and to compare the outcomes with those after isolated ACL reconstruction in patients aged ≤16 years. Patients in our database from 2013 to 2017 were retrospectively analyzed. Patients were assigned to one of two treatment groups based on the presence of BHMTs: no meniscal tear group (group A) and BHMT group (group B). All BHMTs were repaired using the combined inside-out with all-inside technique. This study included 64 knees divided into two groups: 47 knees in group A and 17 knees in group B. There was a significant difference in the interval between ACL injury and surgery between groups A and B (69 vs. 150 days, respectively; P < 0.001). Mean postoperative International Knee Documentation Committee and Lysholm scores in group A were slightly, although significantly, improved compared to those in group B (96.5 vs. 92.6, respectively; P < 0.05, and 98 vs. 95, respectively; P < 0.05). There were no significant differences in postoperative anteroposterior laxity and graft failure rate between the groups. In group B, four patients (23.5%) required surgery for incomplete meniscal healing. Postoperative International Knee Documentation Committee and Lysholm scores of patients with BHMTs were significantly lower than those of patients without any meniscal tear, although with significant improvement in the amount of instability. Level of evidence was Level III.

Promethazine Downregulates Wnt/ß-Catenin Signaling and Increases the Biomechanical Forces of the Injured Achilles Tendon in the Early Stage of Healing.

BACKGROUND: Wnt/ß-catenin signaling suppresses the differentiation of cultured tenocytes, but its roles in tendon repair remain mostly elusive. No chemical compounds are currently available to treat tendon injury. HYPOTHESIS: We hypothesized that the inhibition of Wnt/ß-catenin signaling would accelerate tendon healing. STUDY DESIGN: Controlled laboratory study. METHODS: Tendon-derived cells (TDCs) were isolated from rat Achilles tendons. The right Achilles tendon was injured via a dermal punch, while the left tendon was sham operated. A Wnt/ß-catenin inhibitor, IWR-1, and an antihistamine agent, promethazine (PH), were locally and intramuscularly injected, respectively, for 2 weeks after surgery. The healing tendons were histologically and biomechanically evaluated. RESULTS: The amount of ß-catenin protein was increased in the injured tendons from postoperative weeks 0.5 to 2. Inhibition of Wnt/ß-catenin signaling by IWR-1 in healing tendons improved the histological abnormalities and decreased ß-catenin, but it compromised the biomechanical properties. As we previously reported that antihistamine agents suppressed Wnt/ß-catenin signaling in human chondrosarcoma cells, we examined the effects of antihistamines on TDCs. We found that a first-generation antihistamine agent, PH, increased the expression of the tendon marker genes Mkx and Tnmd in TDCs. Intramuscular injection of PH did not improve histological abnormalities, but it decreased ß-catenin in healing tendons and increased the peak force and stiffness of the healing tendons on postoperative week 2. On postoperative week 8, however, the biomechanical properties of vehicle-treated tendons became similar to those of PH-treated tendons. CONCLUSION: IWR-1 and PH suppressed Wnt/ß-catenin signaling and improved the histological abnormalities of healing tendons. IWR-1, however, compromised the biomechanical properties of healing tendons, whereas PH improved them. CLINICAL RELEVANCE: PH is a candidate repositioned drug that potentially accelerates tendon repair.

Inflammatory effect of advanced glycation end products on human meniscal cells from osteoarthritic knees.

OBJECTIVE: To investigate the inflammatory effects of advanced glycation end-products (AGEs) through the receptor for AGE in meniscal cells from osteoarthritic knees, and examine effects of hyaluronan (HA) on AGE-induced inflammation. METHODS: Meniscal cells from human osteoarthritic knees were cultured with or without glycolaldehyde-AGE-bovine serum albumin and 800 kDa HA. The amount of prostaglandin E(2) (PGE(2)) protein was determined using an enzyme immunoassay system. Expression of cyclooxygenase (COX)-1, COX-2, membrane associated prostaglandin E synthase (mPGES)-1 and cytosolic PGES (cPGES) was analyzed by real-time reverse transcription polymerase chain reaction and western blotting. RESULTS: PGE(2) synthesis was significantly increased by AGEs, and AGE-induced PGE(2) production was attenuated by addition of HA. While COX-2 and mPGES-1 expression was significantly upregulated by AGEs, COX-1 and cPGES expression was not affected by AGE. AGE-stimulated COX-2 and mPGES-1 expression was attenuated by HA through CD44 (HA receptor). However, the changes in COX-1 and cPGES expression were almost negligible. CONCLUSION: In meniscal cells from osteoarthritic knees, AGEs increased the production of inflammatory mediators, including PGE(2), COX-2 and mPGES-1. Furthermore, HA could decrease AGE-induced production of PGE(2), COX-2 and mPGES-1 through CD44.

Geranylgeranylacetone suppresses hydrogen peroxide-induced apoptosis of osteoarthritic chondrocytes.

BACKGROUND: Osteoarthritis (OA) is a common disease, afflicting many sufferers with both pain and functional disorders. Various therapies have been attempted for OA, but no fully effective treatment has been established yet. Apoptosis of chondrocytes caused by reactive oxygen species (ROS) has been considered important in the pathogenesis of OA. The progression of OA may be prevented by suppressing apoptosis of chondrocytes. Geranylgeranylacetone (GGA) has been used as an anti-ulcer drug in Japan for more than 20 years. Several recent studies have shown that GGA can induce heat shock protein (HSP) and exert cytoprotective actions on a large variety of cells and tissues. In this study, we investigated the effects of GGA on the apoptosis of OA chondrocytes induced by hydrogen peroxide (H(2)O(2)). METHODS: Human isolated OA chondrocytes were cultured in the absence or presence of GGA. Cell viability, caspase 3/7 and 9 activities, HSP70 mRNA and protein expressions were examined, and morphological analyses were conducted after exposure of cells to H(2)O(2) to induce apoptosis. RESULTS: Geranylgeranylacetone dose-dependently reversed the H(2)O(2)-induced decrease in cell viability. It was recognized that GGA rendered OA chondrocytes resistant to H(2)O(2)-induced apoptosis from Hoechst 33342 staining and TUNEL staining. Caspases 3 and 9 were activated by addition of H(2)O(2), and GGA suppressed this H(2)O(2)-induced activation of both caspases. H(2)O(2)-induced induction of HSP70 was enhanced in OA chondrocytes by pretreatment with GGA. The results showed that GGA can suppress apoptosis of chondrocytes and enhance production of HSP70. CONCLUSIONS: This study is the first, to our knowledge, to demonstrate that GGA protects OA chondrocytes from H(2)O(2)-induced apoptosis, at least in part by enhancing HSP70 production. These results indicate that GGA is a potentially useful drug for the treatment of OA.

The impact of vitamin D supplementation on body fat mass in elite male collegiate athletes.

BACKGROUND: Whether vitamin D supplementation has any effect on body fat percentage, especially among elite athletes, remains unclear. The aim of this study was to evaluate the effect of vitamin D supplementation on serum vitamin D level in elite male collegiate athletes and to analyze its effect on body fat percentage. METHODS: We enrolled a total of 42 elite male collegiate athletes in this prospective cohort study. In March 2020, body composition monitoring and blood test were performed. All athletes were provided with vitamin D3 supplement tablets of 25 µg/day. The use of the supplement was dependent on athletes' preference. During the study period, their club activities were stopped for 2 months due to the coronavirus disease 2019 outbreak. A second examination, similar to the first one, was performed after approximately 3 months. Supplement usage by each athlete was also confirmed. The participants were divided into a non-supplement group (without supplementation, n = 15) and a supplement group (with supplementation, n = 27). RESULTS: Regarding baseline data at initial examination, the non-supplement and supplement groups showed significant differences in the mean body fat percentage (9.0% and 12.1%, respectively; P = 0.03) and serum 25(OH)D level (22.7 and 18.5 ng/mL, respectively, P = 0.02). At the time of the second examination, there were no significant differences in the results of both the groups. In terms of mean change value from the first to the second examination, there were significant differences in body fat percentage (1.9 and 0.2%, respectively, P = 0.02) and serum 25(OH)D level (1.7 and 7.2 ng/mL, respectively, P < 0.001) between the two groups. A significant negative correlation was observed between the change ratio of body fat percentage and change value of serum 25(OH)D level (r = - 0.37, P = 0.02). CONCLUSIONS: Vitamin D supplementation of 25 µg/day significantly increased the serum 25(OH)D level in elite male collegiate athletes. Vitamin D supplementation may play a role in maintaining athletes' body fat percentage under circumstances where sports activity has decreased.

Assessment of the Preserved Biceps Tendon After Arthroscopic Rotator Cuff Repair in Patients ≤ 55 Years.

PURPOSE: We assessed hypertrophy of preserved long head of the biceps tendon (LHBT) and vascularity in the bicipital groove after arthroscopic rotator cuff repair in ≤55-year-old patients and compared postoperative pain between shoulders with or without vascularity in the bicipital groove. METHODS: Patients who underwent arthroscopic rotator cuff repair between 2015 and 2017 were reviewed. Inclusion criteria were arthroscopic rotator cuff repair and ≤55 years old. Exclusion criteria were a history of contralateral rotator cuff repair, revision surgery, partial repair or superior capsular reconstruction, shoulder dislocation or fracture, torn LHBT at surgery, LHBT tenodesis, retears, <1-year follow-up, and incomplete follow-up data. Cross-sectional area (CSA) of the LHBT and vascularity in the bicipital groove were examined preoperatively and 1 year after surgery using ultrasonography. Shoulder pain at postoperative 1 year was assessed using the pain subscore of the University of California at Los Angeles scale. The data were compared between shoulders with negative and positive vascularity. RESULTS: Fifty-seven shoulders were included in this study. There was no side-to-side difference in preoperative CSA. No difference was found between preoperative and postoperative CSA in the affected shoulders. Postoperative vascularity was identified in 28 (49%) shoulders. Mean pain score was significantly higher in the negative vascularity group than the positive vascularity group (9 and 8, respectively; P = .002). CONCLUSIONS: The preserved LHBT did not show hypertrophy 1 year after arthroscopic repair of medium-sized or smaller posterosuperior rotator cuff tear in ≤55-year-old patients. However, 49% of the shoulders postoperatively demonstrated lower-grade vascularity in the bicipital groove. Healthy LHBT can be preserved in ≤55-year-old patients with posterosuperior medium-sized or smaller rotator cuff tears. LEVEL OF EVIDENCE: III, retrospective comparative prognostic trial.