Article
Biochemistry & Molecular Biology
Fujun Jin, Yexuan Zhu, Meijing Liu, Rongze Wang, Yi Cui, Yanting Wu, Gang Liu, Yifei Wang, Xiaogang Wang, Zhe Ren
Summary: In this study, Babam2 was identified as an essential negative regulator of osteoclast formation and bone resorption. It interacts with Hey1 to inhibit Nfatc1 transcription, thus negatively regulating osteoclastogenesis. Targeting Babam2 may be a novel therapeutic approach for osteoclast-related bone diseases.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yufeng Zhang, Min Yang, Sheng Zhang, Zhiqiang Yang, Yufan Zhu, Yi Wang, Zhe Chen, Xuan Lv, Zan Huang, Yuanlong Xie, Lin Cai
Summary: This study elucidates the importance of the Bhlhe40 gene in osteoclast differentiation and osteoporosis, and identifies the Bhlhe40/c-Fos/Nfatc1 axis as a mechanism involved in regulating osteoclastogenesis. Modulating Bhlhe40 may rescue osteoporosis caused by estrogen deficiency and aging, potentially providing a new therapeutic strategy for the treatment of osteoporosis.
CELL AND BIOSCIENCE
(2022)
Article
Nutrition & Dietetics
Mihyang Kim, Mihwa Park
Summary: This study investigated the effects of I. sinicola extract (ISE) on estrogen deficiency-induced bone loss and osteoclastogenesis. The results showed that ISE improved bone density, trabecular bone structure, and bone biomechanical properties. Moreover, ISE exhibited inhibitory effects on osteoclast formation.
Article
Biochemistry & Molecular Biology
Pedro P. C. de Souza, Petra Henning, Ulf H. Lerner
Summary: Oncostatin M (OSM) is a potent stimulator of osteoclast formation and plays a significant role in bone remodeling by inducing RANKL in osteoblasts. Gene deletion of Osmr in mice leads to decreased osteoclast numbers and increased trabecular bone thickness. OSM can promote osteoblast differentiation and mineralization, but in vivo administration in adult animals does not significantly increase osteoclast formation due to the negative feedback loop through the osteoclastogenesis inhibitor WNT16.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Marta Munar-Bestard, Oscar Villa, Maria del Mar Ferra-Canellas, Joana Maria Ramis, Marta Monjo
Summary: This study describes a simple method for inducing periodontitis in rats. The method involves placing a ligature model around the first maxillary molars and injecting lipopolysaccharide derived from Porphyromonas gingivalis. The induced periodontitis was maintained for 14 days, leading to gingiva recession, alveolar bone loss, and an increase in IL-1 beta levels. This method can be used to study disease progression mechanisms and potential treatments.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Multidisciplinary Sciences
Sabrina Giampaolo, Cristina M. Chiarolla, Konrad Knoepper, Martin Vaeth, Matthias Klein, Azeem Muhammad, Tobias Bopp, Friederike Berberich-Siebelt, Amiya K. Patra, Edgar Serfling, Stefan Klein-Hessling
Summary: In the thymus, the deletion of NFATc1 or its inducible isoforms during the DN stages of thymocyte development leads to an increase in gamma delta thymocytes while alpha beta thymocytes are mostly unaffected. These gamma delta thymocytes upregulate PLZF, the master regulator of NKT cell development, acquiring an NKT gamma delta cell phenotype with higher survival rates. The enhancer E2 is crucial for NFATc1's suppressive function in NKT gamma delta cell formation, translating a strong gamma delta TCR signal into inducible expression of NFATc1 isoforms to control the numbers of NKT gamma delta cells.
Review
Biochemistry & Molecular Biology
Amanda M. Avila-Trejo, Lorena I. Rodriguez-Paez, Veronica Alcantara-Farfan, J. Leopoldo Aguilar-Faisal, Toshio Hattori
Summary: Chronic cases of chikungunya fever pose a public health problem in countries where the virus is present. The disease can persist for years, causing debilitating pain and bone erosion. The mechanisms behind tissue damage and the development of different conditions are not fully understood. This review aims to analyze the molecular and cellular factors that contribute to tissue damage in various infectious conditions caused by the chikungunya virus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Celso M. Queiroz-Junior, Anna C. P. M. Santos, Matheus R. Goncalves, Camila B. Brito, Breno Barrioni, Pedro J. Almeida, Marcela H. Goncalves-Pereira, Tarcilia Silva, Sicilia R. Oliveira, Marivalda M. Pereira, Helton C. Santiago, Mauro M. Teixeira, Vivian V. Costa
Summary: The aim of this study was to investigate the impact of acute coronavirus infection on bone metabolism. The study found that patients with acute COVID-19 had decreased OPG and increased RANKL/OPG ratio in their serum. In vitro experiments showed that coronavirus infection increased the differentiation of macrophages and osteoclasts, as well as TNF release. In vivo experiments in mice showed that coronavirus infection triggered bone resorption and increased the number of osteoclasts, but this effect was not observed in TNFRp55- mice.
Article
Multidisciplinary Sciences
Joao Cardeira-da-Silva, Anabela Bensimon-Brito, Marco Tarasco, Ana S. Brandao, Joana T. Rosa, Jorge Borbinha, Paulo J. Almeida, Antonio Jacinto, M. Leonor Cancela, Paulo J. Gavaia, Didier Y. R. Stainier, Vincent Laize
Summary: By studying the bone patterning during zebrafish fin ray regeneration, it was discovered that the fin rays form through two mineralization fronts and bifurcation is not a simple splitting process. Osteolytic tubules play a key role in defining the position of the branchpoint.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Lidia Ibanez, Josep Nacher-Juan, Maria Carmen Terencio, Maria Luisa Ferrandiz, Maria Jose Alcaraz
Summary: Osteostatin inhibits the differentiation of human osteoclasts and does not affect their resorptive ability. It also controls the differentiation of human osteoclasts by downregulating NFATc1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ling Ji, Xinyi Li, Shushu He, Song Chen
Summary: This review introduces the pathways and related microRNAs involved in osteoclastogenesis, discusses the clinical potential of targeting microRNAs for the treatment of osteoclast-mediated bone resorption, and the challenges of avoiding potential side effects and producing efficient delivery methods.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Simone Tealdi, Elsi Ferro, Carlo Cosimo Campa, Carla Bosia
Summary: In this review, the focus is on microRNA-mediated gene regulatory networks characterized by time-dependent input signals, such as pulses, transient inputs, and oscillations. By identifying the general characteristic of the main motifs underlying temporal patterns, the impact of these patterns on commonly studied oncogenic networks is analyzed, demonstrating how dysfunction can lead to tumorigenesis.
Article
Agronomy
Wei Wang, Shihao Liu, Xin Cheng, Zhenguo Cui, Yabo Jiang, Xianbo Zheng, Bin Tan, Jun Cheng, Xia Ye, Jidong Li, Zhiqian Li, Langlang Zhang, Xiaobei Wang, Haipeng Zhang, Xiaodong Lian, Jiancan Feng
Summary: Ethylene promotes the catabolism of polyamines (PAs) by regulating the expression of the PA oxidase gene PpePAO1, accelerating fruit ripening. The study provides new insights into the crosstalk between ethylene and PAs during fruit ripening.
POSTHARVEST BIOLOGY AND TECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hye Jung Ihn, Jiwon Lim, Kiryeong Kim, Sang-Hyeon Nam, Soomin Lim, Su Jeong Lee, Jong-Sup Bae, Tae Hoon Kim, Jung-Eun Kim, Moon-Chang Baek, Yong Chul Bae, Eui Kyun Park
Summary: Ciclopirox effectively inhibits osteoclast differentiation and bone resorption both in vitro and in vivo, making it a potential candidate for preventing osteoporosis and other osteoclast-related bone diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Jianbo He, Kai Chen, Tiancheng Deng, Jiewei Xie, Kunjing Zhong, Jinbo Yuan, Ziyi Wang, Zhifeng Xiao, Ronghe Gu, Delong Chen, Xiaojuan Li, Dingkun Lin, Jiake Xu
Summary: RH shows significant anti-catabolic effects by inhibiting osteoclastogenesis and bone resorption, potentially through suppressing Nox1 expression, enhancing antioxidant enzyme activity, and inhibiting MAPKs, NF-kappa B, and intracellular Ca2+ oscillation pathways. These findings suggest RH could be a promising natural small molecule for treating osteoporosis by inhibiting excessive osteoclast activity.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Rheumatology
Taro Kasai, Gen Momoyama, Yuichi Nagase, Tetsuro Yasui, Sakae Tanaka, Takumi Matsumoto
Summary: This study suggests that disease activity has an impact on recurrent deformities of the lesser toes in patients with rheumatoid arthritis after resection arthroplasty for forefoot deformities, while recurrent deformities of the hallux are associated with the severity of preoperative hallux deformity.
MODERN RHEUMATOLOGY
(2021)
Review
Endocrinology & Metabolism
Sakae Tanaka, Yoshiya Tanaka
Summary: RANKL plays a critical role in rheumatoid arthritis, with Denosumab being an effective therapeutic option.
JOURNAL OF BONE AND MINERAL METABOLISM
(2021)
Correction
Endocrinology & Metabolism
Sakae Tanaka, Yoshiya Tanaka
Summary: The original publication of the article contained an error in the title of the table, which should have been Baseline patient demographics and characteristics in DESIRABLE trial. This title was adopted from a reference with permission.
JOURNAL OF BONE AND MINERAL METABOLISM
(2021)
Review
Endocrinology & Metabolism
Sakae Tanaka, Toshio Matsumoto
Summary: Sclerostin negatively regulates canonical Wnt signaling pathways by binding to LRP5/6, while Romosozumab, a specific anti-sclerostin antibody, indirectly activates this pathway to promote bone formation.
JOURNAL OF BONE AND MINERAL METABOLISM
(2021)
Article
Endocrinology & Metabolism
Sakae Tanaka, Hideki Mizutani, Eri Tsuruya, Ryoko Fukuda, Kiyoka Kuge, Naoki Okubo
Summary: The study confirmed the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice. It showed significant improvements in bone density and reductions in bone turnover markers, with a low incidence of osteoporotic fractures over 3 years. No new safety signals were identified.
JOURNAL OF BONE AND MINERAL METABOLISM
(2021)
Article
Rheumatology
Uchio Akihiro, Takumi Matsumoto, Yuji Maenohara, Yasunori Omata, Hiroshi Takahashi, Mitsuyasu Iwasawa, Takuo Juji, Ichiro Nakamura, Sakae Tanaka
Summary: The study found that tofacitinib did not suppress the postoperative increase in body temperature and CRP level, but may lead to a decrease in lymphocyte count. The timing for resuming tofacitinib treatment after surgery should be carefully considered.
CLINICAL RHEUMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Takehiro Matsubara, Kazuhito Soma, Ikufumi Yamada, Hiroshi Fujita, Junya Yoshitani, Hiroyuki Oka, Hiroyuki Okada, Sakae Tanaka
Summary: Surgery for intertrochanteric fractures using intramedullary hip nails with an anterior offset (Best Fit Nail) has been found to be more effective in maintaining fragment reduction and proper lag screw position compared with conventional non-offset nails (Proximal Femoral Nail Antirotation), according to postoperative computed tomography evaluation.
Article
Medicine, General & Internal
Takuya Kawahara, Keiko Yamada, Ryohei Terashima, Ikumi Takashima, Sakae Tanaka, Toru Ogata, Hirotaka Chikuda, Hiromasa Miura, Kozo Nakamura, Takashi Ohe
Summary: Multiple imputation was found to be the preferable method for handling missing values in the GLFS-25 questionnaire. However, single imputation using subject average/subject domain average can be used with practically negligible bias as long as the number of missing items is up to 8 out of 25 items in each individual of the population.
Article
Rheumatology
Tsutomu Takeuchi, Sakae Tanaka, Mitsuru Murata, Yoshiya Tanaka
Summary: This study aimed to evaluate the efficacy and safety of TAS5315 in Japanese patients with refractory rheumatoid arthritis. The results showed numerical differences in disease activity improvement rates between the TAS5315 group and the placebo group at week 12, but the primary endpoint was not achieved. However, TAS5315 demonstrated advantages in disease activity and biomarker improvement, as well as higher risk of bleeding events within 36 weeks. Therefore, a risk-benefit analysis of TAS5315 should be considered.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Ryutaro Takeda, Takumi Matsumoto, Yasunori Omata, Hiroshi Inui, Shuji Taketomi, Yuichi Nagase, Takuji Nishikawa, Hiroyuki Oka, Sakae Tanaka
Summary: This study investigated the trend of joint destruction patterns on knee radiographs of patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA) over the past 16 years. The results showed that radiographs of TKA recipients with RA are increasingly presenting osteoarthritic features in recent decades. The study also identified different clusters based on radiographic findings, indicating variations in joint space narrowing, spur formation, and alignment.
CLINICAL RHEUMATOLOGY
(2023)
Article
Orthopedics
H. Kobayashi, N. Ito, Y. Nakai, H. Katoh, K. Okajima, L. Zhang, Y. Tsuda, S. Tanaka
Summary: The aim of this study was to report the patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia (TIO) for early diagnosis. The study included 33 TIO patients treated between January 2000 and June 2022. Symptoms and radiological patterns of insufficiency fractures were investigated. The results showed that TIO patients experienced back pain, chest wall pain, and hip pain, with vertebral fractures being biconcave deformities and periarticular fractures involving subchondral insufficiency fractures and epiphyseal or metaphyseal fractures. The presence of these symptoms and insufficiency fractures in patients with a tumor should suggest TIO diagnosis.
BONE & JOINT JOURNAL
(2023)
Article
Cell & Tissue Engineering
Takeshi Oichi, Joe Kodama, Kimberly Wilson, Hongying Tian, Yuka Imamura Kawasawa, Yu Usami, Yasushi Oshima, Taku Saito, Sakae Tanaka, Masahiro Iwamoto, Satoru Otsuru, Motomi Enomoto-Iwamoto
Summary: Long bone growth in the growth plate relies on endochondral ossification through the accumulation and synthesis of matrix scaffold by chondrocytes. Nutritional restriction increases the number of chondroprogenitors in the resting zone and inhibits their differentiation, while nutrient recovery promotes their differentiation and contributes to accelerated growth. Furthermore, the phosphorylation of Akt in the resting zone is reduced under nutrient deprivation, and exogenous IGF-1 restores the phosphorylation of Akt and stimulates the differentiation of chondroprogenitor cells, leading to a decrease in their numbers.
Article
Endocrinology & Metabolism
Yasunori Omata, Hiroyuki Okada, Steffen Uebe, Naohiro Izawa, Arif B. Ekici, Kerstin Sarter, Taku Saito, Georg Schett, Sakae Tanaka, Mario M. Zaiss
Summary: Bone turnover is regulated by a variety of bone cells, including osteoblasts, osteoclasts, and osteocytes. The differentiation and maturation of osteoclasts are crucial for maintaining skeletal homeostasis. Through single-cell RNA sequencing, researchers identified RAB38 as a key molecule involved in osteoclast differentiation and maturation.
Article
Endocrinology & Metabolism
Hisato Watanabe, Hiroyuki Okada, Jun Hirose, Yasunori Omata, Takumi Matsumoto, Morio Matsumoto, Masaya Nakamura, Taku Saito, Takeshi Miyamoto, Sakae Tanaka
Summary: We investigated the role of hematopoietically expressed homeobox protein (Hhex) in osteoclast development. Our findings suggest that Hhex acts as an inhibitor of osteoclast differentiation through epigenetic regulation and modulation of the cell cycle of osteoclast precursors. Hhex expression is reduced during RANKL-induced osteoclastogenesis, and overexpression or suppression of Hhex affects the development of osteoclasts in vitro. Conditional deletion of Hhex in osteoclast-lineage cells promotes osteoclastogenesis and reduces cancellous bone volume in mice.
Article
Rheumatology
Haruka Tsuchiya, Mineto Ota, Shuji Sumitomo, Kazuyoshi Ishigaki, Akari Suzuki, Toyonori Sakata, Yumi Tsuchida, Hiroshi Inui, Jun Hirose, Yuta Kochi, Yuho Kadono, Katsuhiko Shirahige, Sakae Tanaka, Kazuhiko Yamamoto, Keishi Fujio
Summary: Objectives: Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation in the synovium, where synovial fibroblasts (SFs) play a major role. This study aimed to understand the genetic contribution to molecular regulatory networks in SFs under inflammatory conditions. Methods: SFs from RA and osteoarthritis (OA) patients were stimulated with various cytokines and immune cell subsets were analyzed. Integrative analyses including mRNA expression, histone modifications, 3D genome architecture, and genetic variations were performed. Results: Unstimulated SFs from RA patients showed differences in transcriptome and epigenome compared to OA SFs. Most responses to stimulations were shared between the diseases. SFs expressed pathogenic genes and chromatin remodeling in activated SFs revealed enrichment of RA risk loci in clusters of enhancers induced by proinflammatory cytokines. A RA risk SNP formed 3D contact with the promoter of a gene related to arthritis, and inhibition of this gene suppressed cytokine and chemokine production in SFs. Conclusions: This study identified potential therapeutic targets associated with genetic risk of RA and established a dynamic landscape of activated SFs.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
