Details of a Researcher

A longer duration from injury to surgery is associated with preoperative deterioration of an isolated meniscal tear in patients aged 40 years or older Reviewed

Elective one-stage all four-ligament reconstruction after open knee dislocation: A case report Reviewed

Takuji Yokoe, Takuya Tajima, Nami Yamaguchi, Etsuo Chosa

Journal of Orthopaedic Science 27 ( 3 ) 743 - 749 2022.5

Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.jos.2019.08.012

Yokoe T., Tajima T., Yamaguchi N., Morita Y., Chosa E.

Journal of Orthopaedic Surgery 30 ( 2 ) 10225536221101692 2022.5

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Orthopaedic Surgery

Purpose: To evaluate the preoperative deterioration of an isolated meniscal tear in patients aged 40 years or older, and whether time from injury to surgery is associated with worsening of a meniscal tear. Methods: Patients aged 40 years or older who underwent arthroscopic surgery for isolated meniscal tear between 2014 and 2019 were retrospectively reviewed. The diagnostic magnetic resonance imaging (MRI) findings and arthroscopic findings were compared to evaluate the deterioration of meniscal tears. Predictors of the development of meniscal tears; patient demographic factors, duration from injury to surgery (injury to MRI and MRI to surgery), and image findings were assessed. Results: A total of 58 patients (58 knees) were included (mean age, 55.9 ± 8.5 years; male/female, 31/27). An isolated meniscal tear deteriorated in 28 (48.3%). Compared patients with and without deteriorated meniscal tear, significant differences were found in the MRI grade of meniscal tear (p = 0.03), duration from injury to MRI (164.2 ± 167.9 vs 45.2 ± 48.7 days, p < 0.001), and from MRI to surgery (148.8 ± 91.1 vs 67.6 ± 56.7 days, p < 0.001). A multivariate regression analysis showed that the duration from injury to MRI (odds ratio [OR], 1.03; p < 0.001) and from MRI to surgery (OR, 1.02; p < 0.001) were independent predictors. Conclusion: Approximately 50% of isolated meniscal tears deteriorated preoperatively in patients aged 40 years or older. The duration from injury to surgery was an independent predictor of worsening of an isolated meniscal tear.

DOI： 10.1177/10225536221101692

Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin-Deficient Mice Reviewed

The impact of helicopter emergency medical services and craniocervical traction on the early reduction of cervical spine dislocation in a rural area of Japan Reviewed

Deokcheol Lee, Keisuke Kawano, Shotaro Ishida, Yoichiro Yamaguchi, Tomofumi Kuroki, Takuya Nagai, Kiyoshi Higa, Syuji Kurogi, Hideaki Hamanaka, Hidenobu Ochiai, Etsuo Chosa

Journal of Orthopaedic Science 27 ( 3 ) 606 - 613 2022.4

Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.jos.2021.03.008

Tsuruda T., Yamashita A., Otsu M., Koide M., Nakamichi Y., Sekita-Hatakeyama Y., Hatakeyama K., Funamoto T., Chosa E., Asada Y., Udagawa N., Kato J., Kitamura K.

Journal of the American Heart Association 11 ( 8 ) e025336 2022.4

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of the American Heart Association

BACKGROUND: The biological mechanism of action for osteoprotegerin, a soluble decoy receptor for the receptor activator of nuclear factor-kappa B ligand in the vascular structure, has not been elucidated. The study aim was to determine if osteopro-tegerin affects aortic structural integrity in angiotensin II (Ang II)-induced hypertension. METHODS AND RESULTS: Mortality was higher (P<0.0001 by log-rank test) in 8-week-old male homozygotes of osteoprotegerin gene-knockout mice given subcutaneous administration of Ang II for 28 days, with an incidence of 21% fatal aortic rupture and 23% aortic dissection, than in age-matched wild-type mice. Ang II-infused aorta of wild-type mice showed that osteo-protegerin immunoreactivity was present with proteoglycan. The absence of osteoprotegerin was associated with decreased medial and adventitial thickness and increased numbers of elastin breaks as well as with increased periostin expression and soluble receptor activator of nuclear factor-kappa B ligand concentrations. PEGylated human recombinant osteoprotegerin administration decreased all-cause mortality (P<0.001 by log-rank test), the incidence of fatal aortic rupture (P=0.08), and aortic dissection (P<0.001) with decreasing numbers of elastin breaks, periostin expressions, and soluble receptor activator of nuclear factor-kappa B ligand concentrations in Ang II-infused osteoprotegerin gene-knockout mice. CONCLUSIONS: These data suggest that osteoprotegerin protects against aortic rupture and dissection in Ang II-induced hypertension by inhibiting receptor activator of nuclear factor-kappa B ligand activity and periostin expression.

DOI： 10.1161/JAHA.122.025336

Association between the Beighton Score and Stress Ultrasonographic Findings of the Anterior Talofibular Ligament in Healthy Young Women: A Cross-Sectional Study Reviewed

Yokoe T., Tajima T., Yamaguchi N., Morita Y., Chosa E.

Journal of Clinical Medicine 11 ( 7 ) 2022.4

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Clinical Medicine

The Beighton score (BS) is widely used to evaluate generalized joint laxity. However, the association between the BS and lateral ankle laxity is unclear. This study compared the ultrasono-graphic (US) findings of the anterior talofibular ligament (ATFL) between high-(≥6) and low-(≤3) BS groups of healthy young women. The ATFL lengths of healthy young women were measured in the stress and nonstress positions using the previously reported technique from March 2021 to January 2022. The ATFL ratio (ratio of stress to nonstress ATFL length) was used as an indicator of lateral ankle laxity. The anterior drawer test (ADT) was performed. The correlation between the BS and US findings was also examined. A total of 20 (high-BS group) and 61 (low-BS group) subjects with a mean age of 23.8 ± 1.0 years were included. The high-BS group showed a higher grade of ADT than the low-BS group. No significant differences were found in the nonstress and stress ATFL lengths and ATFL ratio (1.10 ± 0.05 vs. 1.09 ± 0.05, p = 0.19) between the groups. No correlation was found between the BS and US findings. In conclusion, this study did not detect significant differences in the US findings of the ATFL between the high-and low-BS groups.

DOI： 10.3390/jcm11071759

Symptomatic discoid lateral meniscus shows a relationship between types and tear patterns, and between causes of clinical symptom onset and the age distribution Reviewed

Nami Yamaguchi, Etsuo Chosa, Takuya Tajima, Yudai Morita, Takuji Yokoe

Knee Surg Sports Traumatol Arthrosc 30 ( 4 ) 1436 - 1442 2022.4

Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1007/s00167-021-06635-3

学会を聞く第36回日本整形外科学会基礎学術集会

帖佐悦男

整形外科 73 ( 3 ) 283 - 287 2022.3

Publishing type：Research paper (scientific journal) Publisher：南江堂

DOI： 10.15106/j_seikei73_283

Crucial role of high-mobility group box 2 in mouse ovarian follicular development through estrogen receptor beta

Yamaguma Y., Sugita N., Choijookhuu N., Yano K., Lee D., Ikenoue M., Fidya , Shirouzu S., Ishizuka T., Tanaka M., Yamashita Y., Chosa E., Taniguchi N., Hishikawa Y.

Histochemistry and Cell Biology 157 ( 3 ) 359 - 369 2022.3

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Histochemistry and Cell Biology

High-mobility group box 2 (HMGB2) is a chromatin-associated protein that is an important regulator of gene transcription, recombination, and repair processes. The functional importance of HMGB2 has been reported in various organs, including the testis, heart, and cartilage. However, its role in the ovary is largely unknown. In this study, ovary tissues from wild-type (WT) and HMGB2-knock-out (KO) mice were examined by histopathological staining and immunohistochemistry. The ovary size and weight were significantly lower in HMGB2-KO mice than in age-matched WT littermates. Histopathological analysis revealed ovarian atrophy and progressive fibrosis in 10-month-old HMGB2-KO mouse ovaries. Compared to age-matched WT mice, the numbers of oocytes and developing follicles were significantly decreased at 2 months of age and were completely depleted at 10 months of age in HMGB2-KO mice. Immunohistochemistry revealed the expression of HMGB2 in the granulosa cells of developing follicles, oocytes, some corpora lutea, and stromal cells. Importantly, HMGB2-positive cells were co-localized with estrogen receptor beta (ERβ), but not ERα. Estrogen response element-binding activity was demonstrated by southwestern histochemistry, and it was decreased in HMGB2-KO mouse ovaries. Cell proliferation activity was also decreased in HMGB2-KO mouse ovaries in parallel with the decreased folliculogenesis. These results indicated that the depletion of HMGB2 induced ovarian atrophy that was characterized by a decreased ovarian size and weight, progressive fibrosis, as well as decreased oocytes and folliculogenesis. In conclusion, we demonstrated the crucial role of HMGB2 in mouse ovarian folliculogenesis through ERβ expression.

DOI： 10.1007/s00418-022-02074-4

Role of Mel1/Prdm16 in bone differentiation and morphology

原発性骨粗鬆症に対するロモソズマブの実臨床成績の検討 Reviewed

小牧亘, 深野木快士, 太田尾佑史, 福富雅子, 前原孝政, 内村裕起, 大久保節子, 植村貞仁, 帖佐悦男

日本骨粗鬆症学会雑誌 8 ( 1 ) 31 - 43 2022.2

Language：Japanese Publishing type：Research paper (scientific journal)

Kaneda-Nakashima K., Igawa K., Suwanruengsri M., Naoyuki F., Ichikawa T., Funamoto T., Kurogi S., Sekimoto T., Yamashita Y., Chosa E., Yamaguchi R., Morishita K.

Experimental Cell Research 410 ( 2 ) 112969 2022.1

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Experimental Cell Research

MEL1 (MDS1/EVI1-like gene 1/PRDM16), a zinc finger protein, is located near the chromosomal breakpoint at 1p36 in human acute myeloid leukemia (AML) cells with the t (1; 3) (p36; q21) translocation. Mel1/Prdm16 is not only a causative gene of leukemia, but also has multiple regulatory functions, such as the regulation of fat metabolism. To investigate the function of Mel1/Prdm16, we generated Mel1/Prdm16-deficient mice, but homozygous deficiency (Mel1/Prdm16−/−) was embryonic lethal at E 11.5. Heterozygous mice showed abnormal cartilage and bone formation in the postnatal skull and long bones, suggesting that Mel1/Prdm16 expression plays an important role in bone development. In osteoblast and chondrocyte cell lines, Mel1/Prdm16 promotes the differentiation of chondrocytes and regulates the differentiation of osteoblasts. Transient repression of the master regulator Runx2 is required for chondrocyte differentiation at an early stage of differentiation. However, in Mel1/Prdm16-suppressed ATDC5 cells, the initial suppression of Runx2 was lacking and its expression was upregulated at the beginning of differentiation, suggesting that chondrogenic differentiation is suppressed in Mel1/Prdm16+/− mesenchymal progenitor cells because Runx2 expression is upregulated during the early stage of differentiation. Thus, the Mel1/Prdm16 gene may be involved in the early repression of Runx2 expression during osteochondral differentiation and promote chondrogenic differentiation.

DOI： 10.1016/j.yexcr.2021.112969

Action Recognition System for Senior Citizens Using Depth Image Colorization

Htet Y., Zin T.T., Tamura H., Kondo K., Chosa E.

LifeTech 2022 - 2022 IEEE 4th Global Conference on Life Sciences and Technologies 494 - 495 2022

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：LifeTech 2022 - 2022 IEEE 4th Global Conference on Life Sciences and Technologies

This paper describes about the system which can be used at the care center for the purpose of elderly action recognition using depth camera. The depth image colorization is used for compression, visualization, and person detection process. The YOLOv5 (You Only Look Once) algorithm is used as object detector. The space-time features are extracted from depth sequences and they are recognized by linear SVM (Support Vector Machine) classifier. The random image sequences are generated for testing to recognize six actions. The results show that this system can detect the various actions with the average of 92% accuracy for different durations.

DOI： 10.1109/LifeTech53646.2022.9754900

EPLINβ Is Involved in the Assembly of Cadherin-catenin Complexes in Osteoblasts and Affects Bone Formation

Miyazaki Shihoko, Funamoto Taro, Sekimoto Tomohisa, Kurogi Syuji, Ohta Tomomi, Nagai Takuya, Tajima Takuya, Imasaka Mai, Yoshinobu Kumiko, Araki Kimi, Araki Masatake, Choijookhuu Narantsog, Hishikawa Yoshitaka, Chosa Etsuo

ACTA HISTOCHEMICA ET CYTOCHEMICA 55 ( 3 ) 99 - 110 2022

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY

Epithelial protein lost in neoplasm (EPLIN) is an actin-associated cytoskeletal protein that plays an important role in epithelial cell adhesion. EPLIN has two isoforms: EPLINα and EPLINβ. In this study, we investigated the role of EPLINβ in osteoblasts using EPLINβ-deficient (EPLINβGT/GT) mice. The skeletal phenotype of EPLINβGT/GT mice is indistinguishable from the wildtype (WT), but bone properties and strength were significantly decreased compared with WT littermates. Histomorphological analysis revealed altered organization of bone spicules and osteoblast cell arrangement, and decreased alkaline phosphatase activity in EPLINβGT/GT mouse bones. Transmission electron microscopy revealed wider intercellular spaces between osteoblasts in EPLINβGT/GT mice, suggesting aberrant cell adhesion. In EPLINβGT/GT osteoblasts, α- and β-catenins and F-actin were observed at the cell membrane, but OB-cadherin was localized at the perinuclear region, indicating that cadherin-catenin complexes were not formed. EPLINβ knockdown in MC3T3-e1 osteoblast cells showed similar results as in calvaria cell cultures. Bone formation markers, such as RUNX2, Osterix, ALP, and Col1a1 mRNA were reduced in EPLINβ knockdown cells, suggesting an important role for EPLINβ in osteoblast formation. In conclusion, we propose that EPLINβ is involved in the assembly of cadherin-catenin complexes in osteoblasts and affects bone formation.

DOI： 10.1267/ahc.22-00027

Remnant-Preserved Single-Bundle Anterior Cruciate Ligament Augmentation in Multi-ligamentous Knee Reconstruction

Tajima T., Yamaguchi N., Morita Y., Yokoe T., Nagasawa M., Ota T., Kawagoe S., Nakamura Y., Chosa E.

Journal of Knee Surgery 36 ( 10 ) 1095 - 1101 2022

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Knee Surgery

This study was conducted to present remnant-preserving anterior cruciate ligament (ACL) augmentation as a useful option for partial ACL injury in multiligament knee injury (MLKI) cases, which may also contribute to conserving graft resources. The present study involved patients diagnosed with MLKI at our institute from Spring 2006 to February 2021. A total of 71 MLKI cases were provided surgery due to knee instability and disability. For every patient, an arthroscopic diagnostic was performed to ensure that ACL tear and a remnant were present. When the ACL remnant was classified into group 2, 3, or 4 of Nakamae's classification, remnant-preserved single bundle ACL augmentation was performed. Graft selection and the combination of injured ligaments were evaluated. The side-to-side difference under an anterior tibial load of 134 N with an arthrometer and the leg symmetry index at 60 degrees/s were measured. The present procedure was performed for five cases (male/female: 4/1, mean age: 33.6 years). The mean follow-up period was 26.4 months. The combination of torn ligaments was as follows: 3 cases of ACL + medial collateral ligament, one case of ACL + posterior cruciate ligament, and one case of ACL + posterolateral corner. An ACL augmentation graft was performed using an ipsilateral gracilis tendon in 2 cases, a contralateral full semitendinosus tendon in 2 cases, and the ipsilateral distal 1/2 of the semitendinosus tendon in 1 case. The mean side-to-side difference was 1.07 ± 0.4 mm. The mean leg symmetry index was 82.6 ± 12.2% in knee extension and 96.3 ± 9.9% in knee flexion. Although the present study was a small case series, the remnant-preserved single-bundle ACL augmentation for MLKI surgery provided good clinical outcome and conserved the graft resource. Even in the MLKI case, this technique is one of the useful surgical options. The level of evidence of this study is level IV (case series).

DOI： 10.1055/s-0042-1749603

Risk factors of loss of knee range of motion after primary anterior cruciate ligament reconstruction following preoperative recovery of knee range of motion

Yokoe T., Tajima T., Yamaguchi N., Morita Y., Chosa E.

Journal of Knee Surgery 36 ( 13 ) 1365 - 1373 2022

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Knee Surgery

The loss of knee range of motion (ROM) is not an uncommon complication after anterior cruciate ligament reconstruction (ACLR). However, the risk factors of loss of knee ROM remain debatable. The purpose of this study was to evaluate the incidence and risk factors of loss of knee ROM at 12 months after primary ACLR performed after regaining full knee ROM preoperatively. Consecutive patients who underwent primary ACLR after regaining full ROM between January 2014 and January 2020 were retrospectively reviewed. Patients who received a surgical arthrolysis within 12 months after ACLR or those who had a loss of knee ROM at 12 months postoperatively were defined as the loss of ROM group. Possible risk factors of loss of knee ROM, including patient demographic, preoperative, surgical, and postoperative factors, were assessed. The notch wide index and radiographic parameters of the tibial spines; medial tibial spine height (MTSH)/tibial length (TL), lateral tibial spine height (LTSH)/TL, and tibial spine width (TSW)/TL, were also assessed. A total of 141 patients (141 knees) were included (mean age, 25.8 ± 11.4 years; male/female, 56/85). Of the 141 patients, 3 received surgical arthrolysis within 12 months, and 23 had a loss of knee ROM at 12 months after ACLR. Compared patients with and without loss of knee ROM, significant differences were found in the age (p = 0.04), LTSH/TL (p = 0.02), and TSW/TL (p = 0.02). A multivariate regression analysis showed that the age (odds ratio [OR]; 1.05, 95% confidence interval [CI]: 1.01-1.09, p = 0.02), LTSH/TL (OR: 1.44, 95% CI: 1.01-2.1, p = 0.04), and TSW/TL (OR: 0.79, 95% CI: 0.65-0.97, p = 0.02) were identified as significant independent risk predictors of loss of knee ROM. This study showed that the incidence of loss of knee ROM at 12 months after primary ACLR was 18.4% (26/141). An older age, a higher LTSH/TL and a smaller TSW/TL may be associated with loss of knee ROM at 12 months after ACLR.

DOI： 10.1055/a-1934-0776

The anterior talofibular ligament ratio was greater in young men with generalized joint laxity than in those without generalized joint laxity Reviewed

Yokoe T., Tajima T., Yamaguchi N., Morita Y., Chosa E.

Knee Surgery, Sports Traumatology, Arthroscopy 31 ( 5 ) 1994 - 2000 2022

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Knee Surgery, Sports Traumatology, Arthroscopy

Purpose: This study aimed to evaluate the relationship between generalized joint laxity (GJL) and stress ultrasonographic (US) findings of the anterior talofibular ligament (ATFL) of healthy young men. Methods: The ATFL lengths of healthy young men were consecutively measured in the stress and nonstress positions. The ATFL ratio was calculated as an indicator of lateral ankle laxity. GJL was evaluated using the Beighton score (BS), and a BS of ≥ 5 was considered GJL. The manual anterior drawer test (ADT) was also performed. The results of stress US and ADT were compared between subjects with and without GJL, and the correlation between GJL and US findings was examined. Results: A total of 13 subjects with GJL and 95 without GJL were included in the study. The mean BSs in the GJL and no-GJL groups were 5.9 ± 0.9 and 1.1 ± 1.3, respectively (p < 0.0001). The GJL group showed a higher grade of ADT than the no-GJL group (p < 0.0001). Significant differences were found in the stress ATFL length (23.6 ± 1.8 mm vs. 21.7 ± 1.8 mm, p = 0.002) and ATFL ratio (1.15 ± 0.06 vs. 1.07 ± 0.03, p < 0.0001) between the GJL and no-GJL groups. Spearman’s correlation coefficients showed a moderate correlation between the BS and ATFL ratio (r = 0.45, p < 0.0001). Conclusion: The present study showed significant differences in the ATFL ratio and stress ATFL length between young men with and without GJL. The BS was moderately correlated with the lateral ankle laxity in this population. Level of evidence: Level IV.

DOI： 10.1007/s00167-022-07109-w

化膿性肩関節炎後にリバース型人工肩関節全置換術を施行した1例

泉俊彦, 長澤誠, 川越秀一, 大田智美, 帖佐悦男

肩関節 46 ( 1 ) 254 - 257 2022

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：日本肩関節学会

化膿性肩関節炎後の機能障害に対しリバース型人工肩関節全置換術（RSA）を施行する前には，感染制御状態を評価する必要があるがその評価に統一した見解は得られていない．今回74歳男性に対しRSAを実施するにあたり，関節リウマチの併存から感染制御判断に難渋した症例を経験した．現状単一の検査で感染を否定することは困難であるため，総合的な評価を行ったうえでRSAを含めた治療戦略を確立する必要がある

DOI： 10.11296/katakansetsu.46.254

Depletion of high-mobility group box 2 causes seminiferous tubule atrophy via aberrant expression of androgen and estrogen receptors in mouse testis†

Evaluation of a proposed knee brace on the basis of the changes in fot center of pressure and surface electromygraphy of lower limb muscle. Reviewed

Gang DENG　Etsuo CHOSA　Koki OUCHI　Shigeaki MIYAZAKI　Toshiki ABE　Hitonobu KOIKE

43 309 - 318 2022

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Clinical Biomechanics

Remnant-Rreserved Single-Bundle Anterior Cruciate Ligament Augmentation in Multi-ligamentous Knee Reconstruction Reviewed

Takuya Tajima,MD, PhD NamiYamaguchi,MD,PhD Yudai Morita,MD Takuji Yokoe,MD Makotot Nagasawa,MD Tomomi Ota,MD Shuichi Kawagoe,MD Yoshihiro Nakamura, MD Etsuo Chosa,MD,PhD

Thieme 2022

Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1055/s-0042-1749603.

Sugita N., Choijookhuu N., Yano K., Lee D., Ikenoue M., Fidya , Taniguchi N., Chosa E., Hishikawa Y.

Biology of reproduction 105 ( 6 ) 1510 - 1520 2021.12

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Biology of reproduction

High-mobility group box 2, a chromatin-associated protein that interacts with deoxyribonucleic acid, is implicated in multiple biological processes, including gene transcription, replication, and repair. High-mobility group box 2 is expressed in several tissues, including the testis; however, its functional role is largely unknown. Here, we elucidated the role of high-mobility group box 2 in spermatogenesis. Paraffin-embedded testicular tissues were obtained from 8-week-old and 1-year-old wild-type and knock-out mice. Testis weight and number of seminiferous tubules were decreased, whereas atrophic tubules were increased in high-mobility group box 2-depleted mice. Immunohistochemistry revealed that atrophic tubules contained Sertoli cells, but not germ cells. Moreover, decreased cell proliferation and increased apoptosis were demonstrated in high-mobility group box 2-depleted mouse testis. To elucidate the cause of tubule atrophy, we examined the expression of androgen and estrogen receptors, and the results indicated aberrant expression of androgen receptor and estrogen receptor alpha in Sertoli and Leydig cells. Southwestern histochemistry detected decreased estrogen response element-binding sites in high-mobility group box 2-depleted mouse testis. High-mobility group box 1, which has highly similar structure and function as high-mobility group box 2, was examined by immunohistochemistry and western blotting, which indicated increased expression in testis. These findings indicate a compensatory increase in high-mobility group box 1 expression in high-mobility group box 2 knock-out mouse testis. In summary, depletion of high-mobility group box 2 induced aberrant expression of androgen receptor and estrogen receptor alpha, leading to decreased germ cell proliferation and increased apoptosis which resulted in focal seminiferous tubule atrophy.

DOI： 10.1093/biolre/ioab187