A Novel High-Throughput Screening Method for a Human Multicentric Osteosarcoma-Specific Antibody and Biomarker Using a Phage Display-Derived Monoclonal Antibody.

Osteosarcoma is a malignant tumor that produces neoplastic bone or osteoid osteoma. In human multicentric osteosarcoma (HMOS), a unique variant of human osteosarcoma (HOS), multiple bone lesions occur simultaneously or asynchronously before lung metastasis. HMOS is associated with an extremely poor prognosis, and effective treatment options are lacking. Using the proteins in our previously generated HMOS cell lines as antigens, we generated antibodies using a human antibody phage library. We obtained antibody clones recognizing 95 independent antigens and developed a fluorescence probe-based enzyme-linked immunosorbent assay (ELISA) technique capable of evaluating the reactivity of these antibodies by fluorescence intensity, allowing simple, rapid, and high-throughput selection of antibody clones. These results were highly correlated with those using flow cytometry. Subsequently, the HMOS cell lysate was incubated with the antibody, the antigen-antibody complex was recovered with magnetic beads, and the protein bands from electrophoresis were analyzed using liquid chromatography-mass spectrometry (LC/MS). CAVIN1/polymerase I transcript release factor was specifically detected in the HMOS cells. In conclusion, we found via a novel high-throughput screening method that CAVIN1/PTRF is an HMOS-specific cell membrane biomarker and an antigen capable of producing human antibodies. In the future, antibody-drug conjugate targeting of these specific proteins may be promising for clinical applications.

Effects of porous tantalum on periprosthetic bone remodeling around metaphyseal filling femoral stem: a multicenter, prospective, randomized controlled study.

Periprosthetic bone loss due to adaptive bone remodeling is an important unresolved issue in cementless total hip arthroplasty (THA). The use of porous tantalum on the proximal surface of the femoral stem is expected to decrease postoperative bone loss around the prosthesis through early fixation. We conducted a multicenter randomized controlled study to determine if porous tantalum could reduce periprosthetic bone loss after THA. From October 2012 to September 2014, 118 patients (mean age, 61.5 years; 107 females and 11 males) were prospectively enrolled and were randomly allocated at a ratio of 1:1 to either a metaphyseal filling stem with a proximal porous tantalum coating (Trabecular Metal) or a conventional metaphyseal filling stem with fiber mesh coating (VerSys). Patients underwent dual-energy x-ray absorptiometry scans within 1 week after surgery (baseline) and at 6, 12, and 24 months after surgery to assess periprosthetic bone mineral density (BMD) in the 7 Gruen zones. In addition, the Japanese Orthopaedic Association hip score was assessed before surgery and at 6, 12, and 24 months after surgery. In the proximal periprosthetic region (zones 1 and 7), the Trabecular Metal group had significantly smaller reductions in BMD than the VerSys group throughout the study period. In the VerSys group, significant reductions in BMD compared to baseline were seen at each measurement point in all regions, except in zone 6 at 24 months. In the Trabecular Metal group, no significant reductions in BMD relative to baseline were seen in zones 1, 5, or 6 throughout the study period. Both groups demonstrated similar improvement in Japanese Orthopaedic Association hip scores over the study period. This study demonstrated that a proximally coated stem with porous tantalum has superior results over a conventional stem with titanium fiber mesh in terms of periprosthetic bone remodeling.

Impact of musculoskeletal disorders on healthy life expectancy in Japan.

BACKGROUND: Musculoskeletal disorders are a key cause of morbidity in elderly people. How musculoskeletal disorders relate to healthy life expectancy remain elusive. Hence, we aimed to estimate gains in healthy life expectancy from the elimination of musculoskeletal diseases and injuries by using recent national health statistics data in Japan. METHODS: Mortality data were taken from Japanese national life tables and death certificates in 2016. Information on medical diagnoses, injuries, and activity were obtained from the 2016 Comprehensive Survey of Living Conditions. We examined five disorders: rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture. The prevalence of limitations in activities of daily living (ADL) in the population after eliminating the disorder was estimated as the proportion of outpatients without the disorder and ADL limitations, inpatients without the disorder in hospitals and clinics, and people without the disorder who reside in long-term elderly care facilities. RESULTS: There were small gains in life expectancy from elimination of all selected musculoskeletal disorders (0.0-0.1 years). Elimination of rheumatoid arthritis, osteoporosis, and fracture slightly increased the expected years without activity limitation (0.1-0.4) and slightly decreased years with activity limitation (0.1-0.4 years). Meanwhile, elimination of arthrosis, low back pain, and arthrosis and low back pain moderately increased expected years without activity limitation (0.3-1.5 years) and decreased years with activity limitation (0.3-1.5 years). In addition, elimination of rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture decreased expected years with ADL limitations (0.0-0.8 years) and non-ADL limitations (0.0-0.3 years). A combination of arthrosis and low back pain showed a moderate decrease in expected years with both ADL limitations (0.7-1.1 years) and non-ADL limitations (0.3-0.4). CONCLUSIONS: These findings provide clinical evidence that among the musculoskeletal disorders low back pain and arthrosis are the key factors for the elongation of healthy life expectancy.

Desloratadine inhibits heterotopic ossification by suppression of BMP2-Smad1/5/8 signaling.

Heterotopic ossification (HO) is a pathological condition in which ectopic bone forms within soft tissues such as skeletal muscle. Human platelet-derived growth factor receptor α positive (PDGFRα+) cells, which were proved to be the original cells of HO were incubated in osteogenic differentiation medium with Food and Drug Administration-approved compounds. Alkaline phosphatase activity was measured as a screening to inhibit osteogenic differentiation. For the compounds which inhibited osteogenic differentiation of PDGFRα+ cells, we examined dose dependency of its effect using alizarin red S staining and its cell toxicity using WST-8. In addition, regulation of bone morphogenetic proteins (BMP)-Smad signaling which is the major signal of osteogenic differentiation was investigated by Western blotting to elucidate the mechanism of osteogenesis inhibitory effect by the compound. In vivo experiment, complete transverse incision of Achilles tendons in mice was made and mice were fed the compound by mixing with drinking water after operation. Ten weeks after operation, we assessed and quantified HO by micro-computed tomography scan. Intriguingly, we discovered desloratadine inhibited osteogenic differentiation of PDGFRα+ cells using the drug repositioning method. Desloratadine inhibited osteogenic differentiation of the cells dose dependently without cell toxicity. Desloratadine suppressed phosphorylation of Smad1/5/8 induced by BMP2 in PDGFRα+ cells. In Achilles tenotomy mice model, desloratadine treatment significantly inhibited ectopic bone formation compared with control. In conclusion, we discovered desloratadine inhibited osteogenic differentiation using human PDGFRα+ cells and proved its efficacy using Achilles tenotomy ectopic bone formation model in vivo. Our study paved the way to inhibit HO in early clinical use because of its guaranteed safety.

Mesenchymal Bmp3b expression maintains skeletal muscle integrity and decreases in age-related sarcopenia.

Age-related sarcopenia constitutes an important health problem associated with adverse outcomes. Sarcopenia is closely associated with fat infiltration in muscle, which is attributable to interstitial mesenchymal progenitors. Mesenchymal progenitors are nonmyogenic in nature but are required for homeostatic muscle maintenance. However, the underlying mechanism of mesenchymal progenitor-dependent muscle maintenance is not clear, nor is the precise role of mesenchymal progenitors in sarcopenia. Here, we show that mice genetically engineered to specifically deplete mesenchymal progenitors exhibited phenotypes markedly similar to sarcopenia, including muscle weakness, myofiber atrophy, alterations of fiber types, and denervation at neuromuscular junctions. Through searching for genes responsible for mesenchymal progenitor-dependent muscle maintenance, we found that Bmp3b is specifically expressed in mesenchymal progenitors, whereas its expression level is significantly decreased during aging or adipogenic differentiation. The functional importance of BMP3B in maintaining myofiber mass as well as muscle-nerve interaction was demonstrated using knockout mice and cultured cells treated with BMP3B. Furthermore, the administration of recombinant BMP3B in aged mice reversed their sarcopenic phenotypes. These results reveal previously unrecognized mechanisms by which the mesenchymal progenitors ensure muscle integrity and suggest that age-related changes in mesenchymal progenitors have a considerable impact on the development of sarcopenia.

Tibial rotational alignment after opening-wedge and closing-wedge high tibial osteotomy.

A lot of good outcomes have been reported after opening-wedge high tibial osteotomy (OWHTO) and closing-wedge high tibial osteotomy (CWHTO).The purpose of this study was to examine the rotational alignment after OWHTO and CWHTO performed by the same surgeon in one hospital. The sample included 30 knees from 24 patients. In all cases, the same orthopaedic surgeon performed the osteotomy surgeries using the same method. The tibial external rotation angle (TERA) was measured using the CT images of proximal tibial plateau and distal tibial malleolus from the consecutive axial CT slices of tibia. In this study, two considerations were examined. The first was the change in rotation angle, which was defined by TERA noted before and after the operation. The second was the relationship between the correction angle of the osteotomy and the rotation angle change of the distal tibia. The first was evaluated using the paired-Student's t-test, while the second was analyzed with Pearson's correlation coefficient. In the OWHTO group, the mean TERA was 21.4± 7.0° preoperatively and 20.2 ± 8.0° postoperatively, but no significant difference was seen between pre- and post-operation measurements (p = 0.21). Significant TERA increasing (that is, external rotation of the distal tibia) was seen postoperatively in only three knees. In the CWHTO group, the mean TERA was 19.9 ± 10.5° preoperatively and 16.5 ± 9.5° postoperatively, and significant difference was seen between pre- and post-operative TERA (p < 0.05). No significant correlation was seen between the correction angle and the change of the rotation angle in either group (r = 0.40, r = 0.12) . In the OWHTO group, both internal and external rotation of the distal tibia can occur after surgery. In the CWHTO group, the distal tibia rotated internally postoperatively. No significant correlation was seen between the correction angle and the change in the rotation angle in either group.

Retraction: Preventive effects of risedronate and calcitriol on cancellous osteopenia in rats treated with high-dose glucocorticoid.

The following articles have been retracted by the Editorial Board of Experimental Animals, because some parts of their contents were published elsewhere.

Surgical complication and postoperative pulmonary function in patients undergoing tumor surgery with thoracic wall resection.

Postoperative complications of thoracic wall resection include respiratory complications, skin necrosis and infection. The aim of the present study was to examine postoperative complications in patients who required combined thoracic wall resection during the surgical removal of a tumor. The present study included 68 patients; there were 50 patients with lung tumors and 18 patients with musculoskeletal tumors. The clinical factors associated with complications were compared between the two groups. Preoperative and postoperative pulmonary function tests were performed to examine the residual pulmonary function in 16 patients. Thoracic cage reconstruction was performed in 46 patients. Postoperative complications occurred in 30 (44.1%) patients, and one patient died from postoperative pneumonitis. Compared with the pulmonary function preoperative test results, the postoperative results revealed a decrease in the mean vital capacity percentage and an increase in the mean forced expiratory volume within 1 sec as a percent of the forced vital capacity. In patients with lung tumors, pneumonectomy can result in an increased rate of complications following thoracic wall resection. Residual pulmonary function is affected by impaired thoracic cage expansion and removal of the lung. However, the results of the present study demonstrated that these complications can be somewhat stabilized by thoracic wall reconstruction.

Efficacy and risks of fondaparinux 7.5 mg for deep vein thrombosis after total knee arthroplasty.

OBJECTIVES: High-dose fondaparinux therapy at 7.5 mg/day (FPX 7.5 mg) for deep vein thrombosis (DVT) may increase the risk of hemorrhage. We investigated the efficacy and safety of FPX 7.5 mg to treat DVT after total knee arthroplasty. METHODS: This study included 101 patients (91 with osteoarthritis, 10 with rheumatoid arthritis; mean age at total knee arthroplasty: 72.9 years) with asymptomatic postoperative DVT. Medical prophylaxis for DVT was started on postoperative day 1. Vascular ultrasound was conducted within 2 days postoperatively; patients were switched to FPX 7.5 mg after DVT diagnosis. Ultrasound was repeated to monitor DVT resolution. Adverse reactions were assessed. RESULTS: DVT resolved in 72 patients (71.3%) receiving FPX 7.5 mg. There were no significant differences between patients with versus without DVT resolution in the timing of FPX 7.5 mg therapy, treatment period, age, body mass index, or D-dimer or hemoglobin levels. There was no significant difference in DVT outcome between patients starting FPX 7.5 mg within 4 days postoperatively versus on day 5 or later, or between patients treated for ≤7 versus ≥8 days. Hemoglobin decreased to ≤7 g/dL in three patients (2.9%). CONCLUSIONS: FPX 7.5 mg can be expected to resolve DVT in 71.3% of patients; however, the risk of associated hemorrhagic complications may be higher than the risk of pulmonary embolism. To treat DVT with FPX 7.5 mg without compromising safety, patients should be selected carefully and the timing of treatment should be adjusted appropriately.

Is metatarsus primus elevatus truly observed in hallux rigidus? Radiographic study using mapping methods.

BACKGROUND: Hallux rigidus and metatarsus primus elevatus (MPE) are associated, but their causal relationship remains unknown. Several surgical approaches for treating hallux rigidus are available. We evaluated morphological characteristics of hallux rigidus with different grades to determine the optimal surgical approach. The amount of degenerative change in the metatarsophalangeal joint on the preoperative roentgenograms was graded on a scale of 1-3. We analyzed the morphology of hallux rigidus using X-ray image mapping developed by our team. METHODS: This study involved weight-bearing, dorsoplantar, and lateral foot X-rays of 36 feet from 26 patients underwent surgery for hallux rigidus (Group R) at our institution, and 26 normal feet (Group N). A two-dimensional coordinate system was used to analyze the sharps of these feet by converting each dot on the radiographs into X and Y coordinates. Diagrams of the feet from each group were drawn for comparison. Feet with grades 2 (Group R2) and 3 (Group R3) hallux rigidus and normal feet were compared by Kruskal-Wallis test. RESULTS: Mapping revealed that the tip of distal phalanges of the second, and third toes in Group R medially shifted (P < 0.05) in dorsoplantar image of the feet, and that the medial point, a part of the talus, navicular, cuneiform, and first metatarsal bone in Group R, shifted lower (P < 0.05) in lateral feet images of the feet. Multiple comparisons revealed a significant navicular bone depression in grade 3 hallux rigidus compared with normal feet. A significant difference was observed between Group N and R3 but not between Group R2 and N or R3. CONCLUSIONS: X-ray morphological analysis of the foot revealed MPE in Group R. Elevation gradually increased as hallux rigidus grade worsened. Therefore, osteotomy combined with cheilectomy, whereby the first metatarsal bone can be tilted toward the plantar side, are useful for treating a higher-grade hallux rigidus. LEVEL OF EVIDENCE: Level III, comparative study.

Wrist Swelling in Kienböck's Disease.

Background and Purpose Wrist swelling is a frequent clinical manifestation of Kienböck's disease, but no study has reported the site and pathology of wrist swelling in this disease. The aim of this study is to elucidate the site and pathology of wrist swelling in Kienböck's disease. Materials and Methods Dorsal and palmar soft tissue thicknesses of the wrist were measured on standard lateral radiographs of the wrist in 26 patients with Kienböck's disease and 30 subjects without intra-articular lesion. Axial magnetic resonance imaging (MRI) views were examined to detect the site of swelling. The dorsal capsular ligament in three patients with Kienböck's disease underwent histological examination. Results Radiographic study confirmed dorsal wrist swelling in 24 of 26 (92%) patients examined compared with the contralateral unaffected wrists. MRI demonstrated thickening of the dorsal capsular ligament and extensor layer with synovial proliferation. Histological examination revealed nonspecific chronic inflammation. Conclusion Dorsal wrist swelling in Kienböck's disease is a common manifestation and constitutes a part of pathology of Kienböck's disease, although further study is required to clarify the relation between wrist swelling and etiology of Kienböck's disease. Level of Evidence This is a Level III study.

Retraction: Therapeutic effect of risedronate on cancellous and cortical bone in ovariectomized osteopenic rats: a comparison with the effects of alfacalcidol.

The following articles have been retracted by the Editorial Board of Experimental Animals, because some parts of their contents were published elsewhere.

Retraction: Comparative effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats.

The following articles have been retracted by the Editorial Board of Experimental Animals, because some parts of their contents were published elsewhere.

Reliability of radiographic measurement of lateral capitellohumeral angle in healthy children.

This retrospective cohort study was designed to validate the reliability of measurement of the lateral capitellohumeral angle (LCHA), an index of sagittal angulation of the elbow, in healthy children. The results were compared to the Baumann angle (BA), which is a similar concept to LCHA.Sixty-two radiographs of the elbow in healthy children (range, 2-11 years) were reviewed by 6 examiners at 2 sessions. The mean value and reliability of the measurement of LCHA and BA were assessed. Intraobserver reliability and interobserver reliability were calculated using intraclass correlation coefficients (ICCs).The mean LCHA value was 45° (range, 22° to 70°) and the mean BA was 71° (range, 56° to 86°). The ICCs for intraobserver reliability of the LCHA measurements were almost perfect for 2 examiners, substantial for 3 examiners, and moderate for 1 examiner with a mean value of 0.77 (range, 0.57-0.95). For BA measurements, the ICCs were almost perfect for 1 examiner and substantial for 5 examiners with a mean value of 0.74 (range, 0.66-0.83). The ICCs for interobserver reliability between the first and second measurements were both moderate for LCHA (0.56 and 0.51) and for BA (0.52 and 0.50).LCHA showed almost the same reliability in measurement as BA, which is the gold standard assessment for coronal alignment of the elbow. LCHA showed moderate-to-good reliability in the evaluation of sagittal plane elbow alignment.

Efficacy of Chondroitin Sulfate for Painful Knee Osteoarthritis: A One-Year, Randomized, Double-Blind, Multicenter Clinical Study in Japan.

We explored the effects of chondroitin sulfate on knee osteoarthritis in a one-year, randomized, double-blind, dose-comparison study. Patients with painful, Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group) or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index and visual analog scale for pain. We made subgroup analyses according to background symptom severity (Lequesne's index ≥8 or <8) in 73 patients. Serum level of cartilage oligomeric matrix protein and hyaluronic acid were also determined. In the subgroup with severe symptoms (Lequesne's index ≥8), the chondroitin sulfate dose of 1560 mg/d improved pain faster after 6 and 9 months' therapy. However, no dose-related effects were found on cartilage oligomeric matrix protein or hyaluronic acid levels. Chondroitin sulfate also had good tolerability. We conclude that chondroitin sulfate is useful for pain control in knee osteoarthritis.

Sauvé-Kapandji procedure with headless compression screw in patients with rheumatoid arthritis.

OBJECTIVE: We examined the surgical outcomes of the Sauvé-Kapandji (S-K) procedure using a headless compression screw and a metal cancellous screw in patients with rheumatoid arthritis (RA). METHODS: This retrospective study included 41 RA patients who underwent the S-K procedure for distal radioulnar joint disorders with two screws: headless compression screws (HCS group, n = 20) and cannulated cancellous screws (CCS group, n = 21). Clinical and radiographic outcomes were assessed 1 year after surgery. Radiographic outcomes included bony union of the distal radioulnar joint (DRUJ), bone resorption around the screw, a screw back-out, and use of additional K-wire. We investigated any complications related to the screw head. RESULTS: All 20 patients in the HCS group showed bone fusion of the DRUJ. In the CCS group, an asymptomatic non-union was observed in one patient and additional K-wire was needed to stabilize the DRUJ in three patients. No patients complained of any complications related to the screw head in the HCS group, while the CCS group demonstrated the hardware protrusion in two patients who complained of tenderness or discomfort at the screw head. CONCLUSIONS: The use of a headless compression screw in the S-K procedure is useful in patients with RA.

Quantitative assessment of orbital fractures in Asian patients: CT measurement of orbital volume.

Enophthalmos is caused by an increase of orbital volume after blowout fracture and is one of the most critical complications of such fractures, but is often masked by swelling soon after injury. If surgery is performed after swelling resolves, it becomes more difficult to treat enophthalmos because of atrophy and fibrosis. Accordingly, it is important to estimate the severity of enophthalmos soon after injury. We developed a new criterion for determining whether orbital fractures are indicated for surgery in Asian patients using analysis of orbital volume. We retrospectively calculated the orbital volume of patients treated surgically or conservatively and analyzed the correlation between changes of orbital volume and the severity of enophthalmos. Regression analysis of the correlation between enophthalmos and increased orbital volume (y = 0.8x + 0.2; correlation coefficient: 0.92) showed that enophthalmos of 2.0 mm corresponded to an increase in orbital volume of 2.25 cm3. This result is similar to data reported previously for Caucasian patients - enophthalmos of 2.0 mm is a common surgical indication worldwide. Our results suggest that an increase of orbital volume of >2.25 cm3 could be a new criterion for surgical treatment of blowout fractures in Asians.

Acute Compartment Syndrome of Upper Extremities with Tendon Ruptures.

BACKGROUND: It is well known that acute compartment syndrome is associated with fracture of the forearm, while involvement of soft tissue injury including musculotendinous injury remains unclear. The purpose of this study was to evaluate the soft tissue involvement, including musculotendinous ruptures, in acute compartment syndrome of the upper limb. METHODS: We retrospectively enrolled 16 patients who underwent surgical treatment for acute compartment syndrome of the upper extremity. The average age of the patients was 47 years (range, 14 to 79) and the mean follow-up period after the surgery was 15 months (range, 12 to 29). Complications included at least one presentation at the final follow up of sensory disturbances or motor disturbances. We examined the presence of musculotendinous injury mechanism of injury, presence of fracture, the performance of skin grafting, and complications. RESULTS: Mechanism of injury of "caught in a machine" was found in six cases. Three of these patients had musculotendinous ruptures and all muscle tears were revealed by intraoperative findings. No patients had muscle ruptures with other injury mechanisms. Seven out of 16 patients (44%) developed complications at final follow-up. Skin grafting was performed in six patients, and five of these patients developed complications. Only one of the nine patients without complications underwent skin grafting. CONCLUSIONS: In cases of high-energy injuries, the surgeon should suspect the presence of a musculotendinous injury prior to surgery.

Fracture after radiation therapy for femoral metastasis: incidence, timing and clinical features.

We analyzed 428 femoral metastases initially treated with radiotherapy between 2002 and 2011 to clarify the clinical details of post-irradiation fractures of femoral metastasis. Patients included 161 men and 167 women, with a mean age of 62 years. Fracture incidence, fracture site, fracture risk based on X-ray images before radiotherapy, and interval from completion of radiotherapy to fracture occurrence were assessed. In addition, 24 pathological specimens obtained during 27 surgeries for these fractures were examined. Fractures occurred in 7.7% of 428 femoral metastases (total 33: 28 actual fractures and five virtual fractures with progressive pain and bone destruction). The fracture rate was 7.8% in the proximal femur and 1.5% in the shaft (P = 0.001). Fractures occurred a median of 4.4 months after radiotherapy, with 39.4% occurring within 3 months and 63.6% within 6 months. Among femurs with high fracture risk according to Harrington's criteria or Mirels' score, the fracture rate was 13.9% and 11.8%, respectively. Viable tumor cells were detected in all five patients with painful virtual fracture, in 85.7% of femurs with actual fractures that occurred within 3 months, and in only 25.0% of actual fractures occurring after 3 months. Post-irradiation fractures of femoral metastasis most frequently occurred within 3 months after radiotherapy, and were more common in the peritrochanteric area than in the shaft. Radiological evidence of impending fracture did not correlate with a high fracture rate. Actual fractures occurring after more than 3 months were likely caused by post-irradiation fragility of the femur, without viable tumor cells.

Promethazine Hydrochloride Inhibits Ectopic Fat Cell Formation in Skeletal Muscle.

Fatty degeneration of skeletal muscle leads to muscle weakness and loss of function. Preventing fatty degeneration in skeletal muscle is important, but no drug has been used clinically. In this study, we performed drug repositioning using human platelet-derived growth factor receptor α (PDGFRα)-positive mesenchymal progenitors that have been proved to be an origin of ectopic adipocytes in skeletal muscle. We found that promethazine hydrochloride (PH) inhibits adipogenesis in a dose-dependent manner without cell toxicity. PH inhibited expression of adipogenic markers and also suppressed phosphorylation of cAMP response-element binding protein, which was reported to be a primary regulator of adipogenesis. We established a mouse model of tendon rupture with intramuscular fat deposition and confirmed that emerged ectopic adipocytes are derived from PDGFRα+ cells using lineage tracing mice. When these injured mice were treated with PH, formation of ectopic adipocytes was suppressed significantly. Our results show that PH inhibits PDGFRα+ mesenchymal progenitor-dependent ectopic adipogenesis in skeletal muscle and suggest that treatment with PH can be a promising approach to prevent fatty degeneration of skeletal muscle.