Article
Pharmacology & Pharmacy
Jae-Hyun Kim, Minsun Kim, SooYeon Hong, Eun-Young Kim, Hyangsook Lee, Hyuk-Sang Jung, Youngjoo Sohn
Summary: The study demonstrated that albiflorin promotes osteoblastogenesis and the expression of RUNX2 by activating BMP-2/Smad and Wnt/beta-catenin signaling in MC3T3-E1 cells. In the femur fracture model, albiflorin played a positive role in the formation of callus in the early stage of fracture recovery, and induced the expression of osteogenic genes in femur tissue. Additionally, the expression of bone-related genes in serum was increased.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Francesca Manuela Johnson de Sousa Brito, Andrew Butcher, Addolorata Pisconti, Blandine Poulet, Amanda Prior, Gemma Charlesworth, Catherine Sperinck, Michele Scotto di Mase, Ke Liu, George Bou-Gharios, Robert Jurgen van 't Hof, Anna Daroszewska
Summary: Syndecan-3 promotes new bone formation in osteoblasts by enhancing WNT signaling, and its deficiency in mice results in an early osteoporosis-like phenotype due to delayed osteoblast maturation and impaired function. Overexpressing Sdc3 in osteoblasts rescues the low bone volume phenotype and increases bone mass, making SDC3 a potential target for novel bone anabolic drug development.
Article
Critical Care Medicine
Melanie Haffner-Luntzer
Summary: The article explains that fracture healing is a highly coordinated process involving tight interactions of multiple cell types and signaling molecules, with factors affecting fracture healing complexities and the need for improved treatment strategies.
INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED
(2021)
Article
Endocrinology & Metabolism
Kenon Chua, Victor K. Lee, Cheri Chan, Andy Yew, Eric Yeo, David M. Virshup
Summary: The study found that Wnts produced by hematopoietic cells, while not essential, modulate osteoclast numbers during fracture healing, affecting the healing process. This demonstrates the importance of diverse Wnt sources in bone repair.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Chemistry, Medicinal
Junaidi Khotib, Maria Apriliani Gani, Aniek Setiya Budiatin, Maria Lucia Ardhani Dwi Lestari, Erreza Rahadiansyah, Chrismawan Ardianto
Summary: Hydroxyapatite (HA) is widely used in orthopedic and dental applications as a biomaterial that can induce osteoblastic differentiation. Research has shown that the effects of HA involve extracellular signal-regulated kinase, Wnt, and BMP2 factors in cellular regulation.
Article
Biology
Kai Sun, Chun Wang, Jianqiu Xiao, Michael D. Brodt, Luorongxin Yuan, Tong Yang, Yael Alippe, Huimin Hu, Dingjun Hao, Yousef Abu-Amer, Matthew J. Silva, Jie Shen, Gabriel Mbalaviele
Summary: Amino-terminal fragments of proteolytically cleaved GSDMs form plasma membrane pores, leading to pyroptosis. GSDMD and GSDME play roles in bone microenvironment and contribute to fracture healing. Both GSDMD and GSDME regulate inflammatory responses through the GSDM-IL-1 axis, promoting bone healing after fracture.
Article
Medicine, Research & Experimental
P. Kloen, G. G. Loots, R. C. Hamdy, T. H. Smit
Summary: Non-unions of fractured bones are a painful condition that has a significant impact on society and the economy. Surgical intervention, specifically firm compression of bone fragments, is the only treatment option for non-unions. The role of osteocytes and specific molecular pathways in bone healing has been identified in recent years, particularly the RankL/OPG, BMP, and Sclerostin/Dkk1/Wnt axes. Mechanical loading and osteocyte deformation have been found to decrease Sclerostin secretion, leading to activation of the osteogenic Wnt signaling pathway. The hypothesis suggests that osteocytes play a crucial role in non-union healing, and firm compression is necessary to stimulate the osteocytes and promote bone healing.
MEDICAL HYPOTHESES
(2022)
Article
Physiology
Melanie Haffner-Luntzer, Verena Fischer, Anita Ignatius
Summary: The study found that male mice demonstrated faster fracture healing with more prominent cartilaginous callus formation in diaphyseal fractures. This may be attributed to the higher body weight of male mice, resulting in increased mechanical loading at the fracture site. Additionally, male mice exhibited higher activation of osteogenic Wnt/beta-catenin signaling during the fracture healing process.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Orthopedics
Rong Huang, Abhinav R. Balu, Kristin H. Molitoris, James P. White, Alexander G. Robling, Ugur M. Ayturk, Gurpreet S. Baht
Summary: Metrnl plays a crucial role in skeletal development but has little impact on bone fracture healing. The osteoinductive capabilities of Metrnl may be utilized in cell-based orthopedic therapies.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Lena Steppe, Benjamin Thilo Krueger, Miriam Eva Angelica Tschaffon, Verena Fischer, Jan Tuckermann, Anita Ignatius, Melanie Haffner-Luntzer
Summary: Biomechanical stimulation by whole-body low-magnitude high-frequency vibration has shown to have anabolic effects on bone metabolism. Specifically, osteoblast lineage-specific ER alpha plays a critical role in LMHFV-induced effects on fracture healing, with WNT and Cox2/PGE(2) signaling pathways involved in the mechanotransduction process.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Cell & Tissue Engineering
Xiankun Cao, Wenxin He, Kewei Rong, Shenggui Xu, Zhiqian Chen, Yuwei Liang, Shuai Han, Yifan Zhou, Xiao Yang, Hui Ma, An Qin, Jie Zhao
Summary: This study revealed that DZNep enhances osteoblast differentiation and mineralization through the EZH2-H3K27me3-Wnt4 axis, while also promotes osteoclast formation via the EZH2-H3K27me3-Foxc1 axis. This enhanced osteogenesis and osteoclastogenesis resulted in accelerated bone defect healing in mice.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Kento Takaya, Ayano Sunohara, Noriko Aramaki-Hattori, Shigeki Sakai, Keisuke Okabe, Hideko Kanazawa, Toru Asou, Kazuo Kishi
Summary: This study analyzed the expression and localization of Wnt proteins in a mouse fetal-wound-healing model and found their association with scar formation. The results indicated that Wnt signaling may be involved in wound healing and scar formation. Regulation of Wnt signaling could be a possible mechanism to control scar formation.
Article
Pharmacology & Pharmacy
Xiao Yang, Jiang Shao, Xiao-Min Wu, Fei-Fei Pan, Shao-An Yang, Xiao-Hua Pan, An-Min Jin
Summary: Troxerutin, a semi-synthetic derivative of rutin, has been shown to promote osteogenesis in vitro and facilitate fracture healing in vivo, making it a promising therapeutic candidate for bone fracture repair.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sachin Chaugule, Jung-Min Kim, Yeon-Suk Yang, Klaus-Peter Knobeloch, Xi He, Jae-Hyuck Shim
Summary: The study reveals the crucial role of the deubiquitinating enzyme USP8 in promoting Wnt/beta-catenin signaling, which is essential for the differentiation of skeletal stem cells and osteogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
I. Saranya, R. L. Akshaya, N. Selvamurugan
Summary: Bone remodeling involves the coordination of ossification and bone resorption activities by osteoblasts and osteoclasts, regulated by various growth factors and hormones. Dysregulation in the Wnt signaling pathway can lead to bone disorders, with non-coding RNAs playing a critical role in modulating the Wnt cascade for bone homeostasis. Understanding the regulatory role of ncRNAs could provide new therapeutic strategies for bone-related disorders.
Article
Multidisciplinary Sciences
Jian Lei, Abebe Feyissa Amhare, Liyun Wang, Yizhen Lv, Huan Deng, Hang Gao, Xiong Guo, Jing Han, Mikko J. Lammi
SCIENTIFIC REPORTS
(2020)
Article
Medicine, General & Internal
Feng'e Zhang, Mikko Juhani Lammi, Sijia Tan, Peilin Meng, Cuiyan Wu, Xiong Guo
Article
Orthopedics
Jian Lei, Huan Deng, Yan Ran, Yizhen Lv, Abebe Feyissa Amhare, Liyun Wang, Xiong Guo, Jing Han, Mikko J. Lammi
Summary: The study investigated the expression of enzymes involved in synthesis and modification of chondroitin sulfate in knee cartilage tissue of patients with osteoarthritis and Kashin-Beck disease. Results showed damaged morphology, decreased chondrocyte numbers and proteoglycans in OA and KBD groups, as well as lower positive staining rates of aggrecan and CS chain modifying enzymes. These findings suggest that altered expression of these enzymes may contribute to cartilage damage in OA and KBD patients.
Article
Orthopedics
Yanan Zhang, Xiaoli Wei, Chunxia Cao, Fangfang Yu, Wenrong Li, Guanghui Zhao, Haiyan Wei, Feng'e Zhang, Peilin Meng, Shiquan Sun, Mikko Juhani Lammi, Xiong Guo
Summary: Our study found that 10 discriminative features, including changes in bone structure and clinical symptoms, have better diagnostic performance for Kashin-Beck disease in adolescents. These results provide a standard for rapid and effective diagnosis of KBD.
BMC MUSCULOSKELETAL DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Huan Liu, Cuiyan Wu, Hongmou Zhao, Feng'e Zhang, Guanghui Zhao, Xialu Lin, Sen Wang, Xi Wang, Fangfang Yu, Yujie Ning, Lei Yang, Peilong Liu, Feng Zhang, Peng Xu, Chengjuan Qu, Mikko J. Lammi, Xiong Guo
Summary: In this study, a disease-specific human induced pluripotent stem cell (hiPSC) cellular disease model of Kashin-Beck disease (KBD) was successfully established, revealing key dysregulated genes and pathways in KBD. The differentiation of hiPSCs into chondrocytes derived from KBD patients provided insights into the pathogenesis and etiology of KBD, potentially aiding in the development of targeted therapeutics for treatment.
Article
Cell Biology
Xi Wang, Yujie Ning, Pan Zhang, Blandine Poulet, Ruitian Huang, Yi Gong, Minhan Hu, Cheng Li, Rong Zhou, Mikko J. Lammi, Xiong Guo
Summary: Chondrocytes play a key role in the cartilage degeneration of Kashin-Beck disease (KBD) and osteoarthritis (OA). By identifying transcriptional programs and major cell populations in patients with KBD, OA, and healthy controls, the study revealed differences in pathogenetic mechanisms between these two diseases, providing new evidence for understanding the heterogeneity of chondrocytes in KBD and OA.
CELL DEATH & DISEASE
(2021)
Article
Genetics & Heredity
Yanan Zhang, Huan Liu, Xialu Lin, Feng'e Zhang, Peilin Meng, Sijia Tan, Mikko J. Lammi, Xiong Guo
Summary: Kashin-Beck disease (KBD) primarily affects adolescents' growth plates, influenced by both genetic and gene-environmental risk factors. This study demonstrated that HT-2 toxin is an environmental risk factor of KBD, with KBD hiPSC chondrocytes showing stronger responses to HT-2 toxin, leading to damaged organelle ultrastructure, increased G1 phase cells, and late apoptosis.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Luis Oliveros Anerillas, Paul J. Kingham, Mikko J. Lammi, Mikael Wiberg, Peyman Kelk
Summary: Autologous bone transplantation is a common method for reconstructing large bone defects, but has limitations. This study explores the benefits of culturing bone marrow-derived mesenchymal stem cells (BMSCs) in 3D compared to traditional 2D culture. Findings suggest that type I collagen gels are suitable for 3D osteogenic differentiation of BMSCs, potentially enhancing the production of tissue-engineered constructs for bone defect treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Xi Wang, Yujie Ning, Cheng Li, Yi Gong, Ruitian Huang, Minhan Hu, Blandine Poulet, Ke Xu, Guanghui Zhao, Rong Zhou, Mikko J. Lammi, Xiong Guo
Summary: The study aimed to improve understanding of the gut microbiota structure in KBD patients and its relationship with serum metabolites, identifying significant differences in abundant genera between KBD patients and normal controls. The analysis revealed that differences in metabolite levels were associated with altered abundances of specific species, suggesting a novel interplay between gut microbiome and metabolome in KBD pathogenesis.
CELL DEATH & DISEASE
(2021)
Article
Genetics & Heredity
Yujie Ning, Minhan Hu, Jiayu Diao, Yi Gong, Ruitian Huang, Sijie Chen, Feiyu Zhang, Yanli Liu, Feihong Chen, Pan Zhang, Guanghui Zhao, Yanhai Chang, Ke Xu, Rong Zhou, Cheng Li, Feng Zhang, Mikko Lammi, Xi Wang, Xiong Guo
Summary: The genetic polymorphisms of PPARG, ADAM12, IL6, SMAD3, and TIMP2 may contribute to the risk of KBD by disturbing ECM homeostasis.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Yizhen Lyu, Huan Deng, Chengjuan Qu, Lichun Qiao, Xuan Liu, Xiang Xiao, Jiaxin Liu, Ziwei Guo, Yan Zhao, Jing Han, Mikko J. Lammi
Summary: This study aimed to investigate the pathological mechanism of Kashin-Beck disease (KBD) compared with osteoarthritis (OA) by identifying crucial proteins and N-glycosylated sites. Proteomic and N-glycoproteomic analysis revealed differentially expressed proteins and N-glycosylation sites associated with KBD pathological processes. Key pathways were also identified. The findings suggested that N-glycosylation may influence the integrity of chondrocytes or cartilage and contribute to cartilage destruction in KBD.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Cell Biology
Jing Han, Huan Deng, Yizhen Lyu, Xiang Xiao, Yan Zhao, Jiaxin Liu, Ziwei Guo, Xuan Liu, Lichun Qiao, Hang Gao, Mikko Juhani Lammi
Summary: This study aimed to compare the type and content of glycoproteins in the knee cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) patients. Significant differences were found in the expression of key glycoproteins between the two diseases, which were closely related to their pathogenic mechanisms. These findings contribute to a better understanding of the development of OA and KBD, and provide new targets for disease treatment.
Editorial Material
Genetics & Heredity
Mikko J. Lammi, Xi Wang, Yujie Ning
FRONTIERS IN GENETICS
(2023)
Article
Rheumatology
Yujie Ning, Minhan Hu, Yi Gong, Ruitian Huang, Ke Xu, Sijie Chen, Feiyu Zhang, Yanli Liu, Feihong Chen, Yanhai Chang, Guanghui Zhao, Cheng Li, Rong Zhou, Mikko J. Lammi, Xiong Guo, Xi Wang
Summary: This study compared the gut microbiota structure between OA and KBD patients and identified significant differences between the two groups. These findings provide insights into the mechanisms underlying the pathogenesis of OA and KBD.
ARTHRITIS RESEARCH & THERAPY
(2022)
Article
Medicine, General & Internal
Sen Wang, Zongqiang Gao, Huan Liu, Peilin Meng, Cuiyan Wu, Mikko J. Lammi, Xiong Guo
TURKISH JOURNAL OF MEDICAL SCIENCES
(2020)
Review
Endocrinology & Metabolism
Jemima E. Schadow, David Maxey, Toby O. Smith, Mikko A. J. Finnila, Sarah L. Manske, Neil A. Segal, Andy Kin On Wong, Rachel A. Davey, Tom Turmezei, Kathryn S. Stok
Summary: This study systematically reviewed the published parameters for assessing subchondral bone in human osteoarthritis using computed tomography. The study identified clinically meaningful parameter categories and emphasized the importance of quantification and standardized measurement methods for improving the evaluation of disease progression.
Article
Endocrinology & Metabolism
Lindsay L. Loundagin, Kim D. Harrison, Xuan Wei, David M. L. Cooper
Summary: This study developed new techniques to define zones of BMU activity based on the 3D morphology of remodeling spaces in rabbit cortical bone and integrated morphological data with the BMU longitudinal erosion rate (LER) to elucidate the spatial-temporal coordination of BMUs and estimate mineral apposition rate (MAR). The results showed that the manual and semi-automated methods accurately defined the zones of remodeling spaces, and these techniques have the potential to assess dynamic parameters of bone resorption and formation.
Article
Endocrinology & Metabolism
Soroush Masrouri, Farzad Esmaeili, Maryam Tohidi, Fereidoun Azizi, Farzad Hadaegh
Summary: This study examined the association between estimated glomerular filtration rate (eGFR) decline and fracture incidence. The results showed that rapid kidney function decline (RKFD) can increase the incidence of fractures among the general population.
Article
Endocrinology & Metabolism
Steven J. Meas, Gabriella M. Daire, Michael A. Friedman, Rachel Denapoli, Preetam Ghosh, Joshua N. Farr, Henry J. Donahue
Summary: Age- and disuse-related bone loss both lead to decreases in bone mineral density, cortical thickness, and trabecular thickness and connectivity. It is important to experimentally compare these two mechanisms at a structural and transcriptomic level to better understand their similarities and differences. This study compares the effects of hindlimb unloading and aging on bone microarchitecture and gene expression in mice, finding that while both induce similar changes, aging has a greater impact on the transcriptome and tissue level.
Correction
Endocrinology & Metabolism
Masaru Matsuoka, Sho Tsukamoto, Yuta Orihara, Rieko Kawamura, Mai Kuratani, Nobuhiko Haga, Kenji Ikebuchi, Takenobu Katagiri
Article
Endocrinology & Metabolism
Rachel Kohler, Amy Creecy, David R. Williams, Matthew R. Allen, Joseph M. Wallace
Summary: Osteogenesis imperfecta is a hereditary bone disease that weakens bones and increase fracture risk. Current interventions mainly focus on increasing bone mass, but the compromised tissue-level material properties are not addressed. A study found that a RAL analog could reduce fracture risk, but further development is needed for optimal results in patients with osteogenesis imperfecta.
Article
Endocrinology & Metabolism
So Jeong Park, Eunhye Ji, Hyun Ju Yoo, Kyunggon Kim, Sunghwan Ji, Ji Yeon Baek, Jin Young Lee, Hee-Won Jung, Il-Young Jang, Eunju Lee, Namki Hong, Beom-Jun Kim
Summary: The study analyzed the relationship between serum lumican levels and osteosarcopenia in older adults, showing that older adults with osteosarcopenia had lower serum lumican levels. Lower serum lumican levels were associated with reduced bone mass and grip strength, indicating that lumican levels could be used as a biomarker for assessing the risk of osteosarcopenia, osteoporosis, or sarcopenia in older adults.
Article
Endocrinology & Metabolism
Michael B. Chavez, Michelle H. Tan, Tamara N. Kolli, Natalie L. Andras, Brian L. Foster
Summary: This study revealed the complex mechanisms by which disabling BSP functional domains led to profound and distinct changes in cementoblast cell functions, including dysregulated gene expression and reduced mineralization.
Article
Endocrinology & Metabolism
Julien Seiller, Blandine Merle, Romain Fort, Emilie Virot, Solene Poutrel, Giovanna Cannas, Arnaud Hot, Roland Chapurlat
Summary: The purpose of this study was to assess the prevalence of bone fragility in sickle cell patients and to evaluate the potential risk factors and associated complications.
Article
Endocrinology & Metabolism
Chirantap Oza, Anuradha Khadilkar, Pranay Goel, Madhura Karguppikar, Nikhil Shah, Nikhil Lohiya, Shruti Mondkar, Prashant Patil, Hemchand Prasad, Ankita Maheshwari, Dipali Ladkat, Neha Kajale, Chidvilas More, Devarati Khurjekar, Vaman Khadilkar
Summary: This study revealed that BoneXpert (BX) can be used for accurate assessment of bone age and screening of bone health in Indian children and youth with type-1 diabetes (T1D). 51.5% of T1D subjects showed significantly decreased metacarpal index (MCI). Height, Tanner stage, and vitamin D concentrations were positively correlated with MCI, while HbA1c and disease duration were negatively correlated with MCI.
Article
Endocrinology & Metabolism
Mariam R. Farman, Catherine Rehder, Theodora Malli, Cheryl Rockman-Greenberg, Kathryn Dahir, Gabriel Angel Martos-Moreno, Agnes Linglart, Keiichi Ozono, Lothar Seefried, Guillermo del Angel, Gerald Webersinke, Francesca Barbazza, Lisa K. John, Sewmi M. A. Delana Mudiyanselage, Florian Hoegler, Erica Burner Nading, Erin Huggins, Eric T. Rush, Ahmed El-Gazzar, Priya S. Kishnani, Wolfgang Hoegler
Summary: The ALPL gene variant database serves as an archive for interpreting the clinical significance of ALPL gene variants, facilitating the reclassification of VUS and continuous updates. The project establishes an international expert consortium, providing a multidisciplinary collaboration framework to improve genetic counseling and medical decision-making for HPP patients.
Article
Endocrinology & Metabolism
Giovanni Adami, Davide Gatti, Maurizio Rossini, Alessandro Giollo, Matteo Gatti, Francesco Bertoldo, Eugenia Bertoldo, Amy S. Mudano, Kenneth G. Saag, Ombretta Viapiana, Angelo Fassio
Summary: Certain diseases requiring glucocorticoids are independently associated with an increased risk of fractures. Chronic obstructive pulmonary disease (COPD) and neurological diseases are associated with both vertebral and non-vertebral fracture risk, while rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) are only associated with non-vertebral fractures.
Article
Endocrinology & Metabolism
Frank C. Ko, Rong Xie, Brandon Willis, Zoe G. Herdman, Bryan A. Dulion, Hoomin Lee, Chun-do Oh, Di Chen, D. Rick Sumner
Summary: Intramembranous bone regeneration is important in joint and tooth replacement, but its underlying mechanisms are not well understood. This study found that increased periostin gene expression preceded increases in osteogenic genes during bone regeneration. Using a genetic mouse model, the researchers discovered that cells transiently expressing periostin played a critical role in intramedullary intramembranous bone regeneration.
Article
Endocrinology & Metabolism
T. Savikangas, T. H. Suominen, M. Alen, T. Rantalainen, S. Sipila
Summary: Regular exercise, especially high-intensity physical activity, can help slow down age-related bone loss and prevent a decline in femoral neck bone mineral density.
Article
Endocrinology & Metabolism
Mishaela R. Rubin, Ruban Dhaliwal
Summary: The increased risk of fractures observed in adults with type 1 diabetes (T1D) cannot be solely explained by modest decreases in areal bone mineral density (BMD). Accumulation of advanced glycation endproducts (AGEs) in bone has been suggested as a possible cause for the increased bone fragility in diabetes. Although the evidence linking AGEs and fractures in individuals with T1D is limited, recent data show that AGEs, as measured by skin intrinsic fluorescence, are a risk factor for lower BMD in T1D. Further research is needed to determine if there is a causal relationship between fractures and AGEs in T1D. If confirmed, this could lead to interventions that can reduce AGE accumulation and ultimately reduce fractures in T1D patients.