Sites of flexor-pronator muscle injury and relationship between ulnar collateral ligament injury and flexor-pronator muscle injury in baseball players: a retrospective cohort study.

BACKGROUND: Ulnar collateral ligament (UCL) and flexor-pronator muscle (FPM) injuries are common in baseball players. However, the sites of FPM injuries and the relationship between UCL and FPM injuries in baseball players have not been fully clarified. The purpose of this study was to identify the sites of FPM injuries and to determine the relationships of location and severity of UCL injury with the presence of FPM injuries in baseball players. METHODS: UCL and FPM injuries were diagnosed using magnetic resonance imaging in 99 baseball players. The sites of FPM injuries were identified on coronal, sagittal, and axial images. UCL injury severity was classified into four grades: chronic changes, low-grade partial tear, high-grade partial tear, and complete tear. UCL injury location was classified as proximal UCL tear or distal UCL tear. All images were assessed by a musculoskeletal radiologist and an orthopedic surgeon. RESULTS: Combined UCL and FPM injuries were observed in 45 of 99 players, of which 40 of 45 (89%) involved injury of the flexor digitorum superficialis (FDS). All FDS injuries were in the deep layer of the muscle belly. There was no significant difference between the severity of UCL injury and presence of FPM injuries (P = .352). There was a significant association of distal UCL tears with FPM injuries (P < .001). CONCLUSION: FDS injury occurs most commonly in the muscle belly of the second and fifth digits. There may be no relationship between the severity of UCL injury and presence of FPM injury in baseball players. FPM injuries may be a contributing factor in the failure of nonoperative management of distal UCL tears in baseball players.

A Prospective, Randomized, Controlled Trial Comparing Conservative Treatment With Trunk Stabilization Exercise to Standard Hip Muscle Exercise for Treating Femoroacetabular Impingement: A Pilot Study.

OBJECTIVE: To assess the efficacy of conservative management of women with femoroacetabular impingement (FAI) using trunk stabilization. DESIGN: Randomized controlled trial (level of evidence: I). SUBJECTS: Twenty FAI female patients who met the inclusion FAI criteria. METHODS: A prospective, randomized, controlled study was performed on 20 female patients with symptomatic FAI comprising 2 groups (10 hips in trunk stabilization exercise group vs 10 hips in control group). We evaluated hip range of motion, isometric muscle strength using a handheld dynamometer (µ-TasMF-01; Anima, Co), and patient-reported outcome measures, including modified Harris hip score, Vail hip score, and international hip outcome tool 12 (iHOT12) before and at 4 weeks and 8 weeks after the intervention. RESULTS: There was a significant improvement in the range of motion of hip flexion in the trunk training group detected as early as 4 weeks after the intervention compared with the control group (P < 0.05). Hip abductor strength significantly improved in the trunk training group at 4 weeks after the intervention, whereas it did not improve in the control group (P < 0.05). Vail hip score and iHOT12 were significantly increased at 8 weeks after the intervention in the trunk training group compared with the control group (iHOT12: 78.7 ± 22.4 vs 53.0 ± 22.3; P < 0.01, Vail hip score: 81.6 ± 18.5 vs 61.1 ± 11.6; P < 0.05). There was no significant difference in the modified Harris hip score between both the groups at 4 and 8 weeks after the intervention. CONCLUSIONS: The addition of trunk stabilization exercise to a typical hip rehabilitation protocol improves short-term clinical outcomes and may augment nonoperative and postoperative rehabilitation.

Hip Arthroscopic Osteochondral Autologous Transplantation for Treating Osteochondritis Dissecans of the Femoral Head.

Osteochondritis dissecans (OCD) of the femoral head is not a common source of hip pain. Hip arthroscopy is becoming a more frequent indication for intra-articular pathologies of the hip. Osteochondral autologous transplantation is a promising technique that theoretically can reconstruct osteochondral lesions of the femoral head. We describe our technique for arthroscopic antegrade osteochondral autologous transplantation for the treatment of OCD of the femoral head. The advantages of this technique include that it is a less invasive method with the ability to assess and treat intra-articular pathologies associated with OCD of the femoral head at same time. Case series and outcomes after this technique are not currently reported in the literature; however, it could be a less invasive method and provide favorable clinical outcomes for patients with OCD lesions of the femoral head.

Homeostasis of hyaluronic acid in normal and scarred vocal folds.

OBJECTIVES/HYPOTHESIS: Vocal fold scarring is one of the most challenging laryngeal disorders to treat. Hyaluronic acid (HA) is the main component of lamina propria, and it plays an important role in proper vocal fold vibration and is also thought to be important in fetal wound healing without scarring. Although several animal models of vocal fold scarring have been reported, little is known about the way in which HA is maintained in vocal folds. The purpose of this study was to clarify the homeostasis of HA by examining the expression of hyaluronan synthase (Has) and hyaluronidase (Hyal), which produce and digest HA, respectively. STUDY DESIGN: Experimental prospective animal study. METHODS: Vocal fold stripping was performed on 38 Sprague-Dawley rats. Vocal fold tissue was collected at five time points (3 days-2 months). Expression of HA was examined by immunohistochemistry, and messenger RNA (mRNA) expression of Has and Hyal was examined by real-time polymerase chain reaction and in-situ hybridization. RESULTS: In scarred vocal folds, expression of Has1 and Has2 increased at day 3 together with expression of HA and returned to normal at 2 weeks. At 2 months, Has3 and Hyal3 mRNA showed higher expressions than normal. CONCLUSIONS: Expression patterns of Has and Hyal genes differed between normal, acute-scarred, and chronic-scarred vocal folds, indicating the distinct roles of each enzyme in maintaining HA. Continuous upregulation of Has genes in the acute phase may be necessary to achieve scarless healing of vocal folds.

Flt-1 tyrosine kinase-deficient homozygous mice result in decreased trabecular bone volume with reduced osteogenic potential.

To clarify the role of Fms-like tyrosine kinase-1 (Flt-1) signaling in bone dynamics, we examined C57BL/6J mice, aged 6, 9 and 16 weeks, with disruption of the flt1 tyrosine kinase domain gene (flt1(TK-/-)) and compared with age-matched wild-type (flt1(TK+/+)) mice. Dynamic histomorphometric analysis confirmed a significant decrease in the values of mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS) in the trabecular bone of the proximal tibiae of flt1(TK-/-) mice compared with those in flt1(TK+/+) mice. The value of trabecular bone volume (BV/TV) was also significantly reduced in flt1(TK-/-) mice compared with that in flt1(TK+/+) mice. The values of osteoclast surface (Oc.S/BS) and osteoclast number (Oc.N/BS) in flt1(TK-/-) mice were somewhat lower than those in flt1(TK+/+) mice. The values of bending load of the femur significantly decreased in flt1(TK-/-) mice. In addition, serum osteocalcin significantly decreased in flt1(TK-/-) mice compared with those in flt1(TK+/+) mice. Furthermore, there was a significant decreased mineralization of bone marrow stromal cultures from flt1(TK-/-) mice. These findings demonstrate that flt1(TK-/-) mice show lower trabecular bone volume than flt1(TK+/+) mice, providing powerful evidence that vascular endothelial growth factor signal pathway through the Flt-1 tyrosine kinase domain could be implicated in osteoblast development.

Perspectives on mechanisms of gene regulation by 1,25-dihydroxyvitamin D3 and its receptor.

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) functions as a systemic signal in vertebrate organisms to control the expression of genes whose products are vital to the maintenance of calcium and phosphorus homeostasis. This regulatory capability is mediated by the vitamin D receptor (VDR) which localizes at DNA sites adjacent to the promoter regions of target genes and initiates the complex events necessary for transcriptional modulation. Recent investigations using chromatin immunoprecipitation techniques combined with various gene scanning methodologies have revealed new insights into the location, structure and function of these regulatory regions. In the studies reported here, we utilized the above techniques to identify key enhancer regions that mediate the actions of vitamin D on the calcium ion channel gene TRPV6, the catabolic bone calcium-mobilizing factor gene RankL and the bone anabolic Wnt signaling pathway co-receptor gene LRP5. We also resolve the mechanism whereby 1,25(OH)(2)D(3) autoregulates the expression of its own receptor. The results identify new features of vitamin D-regulated enhancers, including their locations at gene loci, the structure of the VDR binding sites located within, their modular nature and their functional activity. Our studies suggest that vitamin D enhancers regulate the expression of key target genes by facilitating the recruitment of both the basal transcriptional machinery as well as the protein complexes necessary for altered gene expression.

The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25-dihydroxyvitamin D3 in intestinal cells.

Transient receptor potential vanilloid type 6 (TRPV6) (ECAC2, CaT1) is the major ion channel in intestinal epithelial cell membranes responsible for calcium entry. Its expression is actively regulated at the transcriptional level by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. In this report, we identify mechanisms integral to the regulation of TRPV6 by 1,25-(OH)2D3. Based upon the hormonal responsiveness of a 7-kb TRPV6 promoter fragment in intestinal cell lines, we used a chromatin immunoprecipitation (ChIP) scanning method to search for possible vitamin D receptor (VDR) and retinoid X receptor (RXR) regulatory regions within the TRPV6 locus. VDR/RXR binding was broad, ranging from -1.2 to -5.5 kb relative to the start site of TRPV6 transcription. These results were consistent with an in silico analysis that revealed putative regulatory elements (VDREs) located at -1.2, -2.1, -3.5, -4.3, and -5.5 kb. Despite the ChIP analyses, only regions of the TRPV6 gene that contained putative elements at -2.1 and -4.3 kb transferred 1,25-(OH)2D3 response to a heterologous promoter. Further study revealed that each of these two active regions contained composite VDREs comprised of two separate regulatory elements. Mutagenesis of the VDREs within the -2.1- and -4.3-kb region and the VDRE at -1.2 kb abrogated all response to 1,25-(OH)2D3 when examined within the natural TRPV6 promoter. A final ChIP assay revealed that VDR/RXR heterodimer binding to the TRPV6 gene was accompanied by both the recruitment of steroid receptor coactivator 1 as well as a broad change in histone 4 acetylation. These studies identify a mechanism by which 1,25-(OH)2D3 regulates the expression of TRPV6 in human intestinal cells.

Vascular endothelial growth factor is expressed along with its receptors during the healing process of bone and bone marrow after drill-hole injury in rats.

In this study, we investigated the expression of vascular endothelial growth factor (VEGF) mRNA along with its receptors in the healing process following rat femoral drill-hole injury. The cellular events involved in the differential expression of VEGF were studied by reverse transcription-polymerase chain reaction, immunocytochemistry, and in situ hybridization. Abundant alkaline phosphatase-positive osteoprogenitor cells were present in the bone marrow cavity surrounding the wound region at day 3. Some of the cells were immunoreactive for Flk-1, a marker of angioblasts. At day 5, osteoblasts expressing osteocalcin mRNA actively participated in bone formation. After day 11, medullary bone gradually decreased and hematopoietic cells covered the wound region. The expressions of the VEGF splice variants VEGF120 and VEGF164 were detected at days 1 and 3, and VEGF188 mRNA began to appear from day 5. The expressions of the three VEGF splice variants gradually decreased after day 11. VEGF immunoreactivity and mRNA expression were strongly detected in angioblasts, osteoprogenitor cells, and osteoblasts between days 3 and 7, but gradually decreased after day 11. Immunoreactivity for Flt-1 was also detected in endothelial cells, osteoprogenitor cells, and osteoblasts between days 3 and 7. However, immunoreactivity for Flk-1 was not detected on osteoblasts but rather on endothelial cells. These findings indicate that the differential expression of VEGF splicing isoforms along with its receptors may play an important role in the healing process after rat femoral drill-hole injury.

[Regulation of bone mass for skeletal loading].

Skeletal loading plays an important role in the maintenance of bone mass, bone shape and bone strength. Skeletal unloading, such as during space flight and long-term bed rest, induces bone loss in loaded bones in humans. The mechanotransduction system in bone tissue is not fully elucidated. Our observations demonstrate that generation of nitric oxide through inducible nitric oxide synthase is essential for the stimulation of bone formation upon mechanical reloading, and that disruption of p53 gene in response to 1-week unloading does not result in reductions in bone volume and bone formation. It should be significantly helpful for our understanding of various skeletal disorders to clarify the mechanism underlying regulation of bone mass after skeletal loading and unloading.

Role of inducible nitric oxide synthase in skeletal adaptation to acute increases in mechanical loading.

To clarify the role of nitric oxide (NO) in regulation of bone metabolism in response to skeletal loading, we examined inducible NO synthase (iNOS) gene knockout mice in the tail-suspension model. Histomorphometric analyses of proximal tibias revealed that 7 days of tail suspension decreased the bone volume (BV/TV) and bone formation rate (BFR/BS) and increased the osteoclast surface (Oc.S/BS) in mice with all iNOS genotypes. Both iNOS+/+ and iNOS+/- mice responded to subsequent 14-day reloading, with increases in BV/TV and BFR/BS and a decrease in Oc.S/BS, whereas these responses were abolished in iNOS-/- mice. The osteoblasts flattened after tail suspension appeared cuboidal during subsequent reloading. Immunoreactivity for iNOS was detected in these osteoblasts and osteocytes by immunohistochemistry. These defective responses after reloading were rescued in iNOS-/- mice by treatment with an NO donor nitroglycerine (NG). Conversely, the responses in iNOS+/+ mice were inhibited by treatment with an NOS inhibitor aminoguanidine (AG). In bone marrow cell cultures, mineralized nodules derived from iNOS-/- mice after reloading were significantly reduced. Taken together, our results suggest that NO generated by iNOS in osteoblasts plays a critical role in adjusting bone turnover and increasing osteogenic activity in response to the acute increase in mechanical loading after tail suspension.