Article
Engineering, Biomedical
Mingsheng Xie, Yiqian Zhang, Zixuan Xiong, Sophie Hines, Jiangyinzi Shang, Karen L. Clark, Susheng Tan, Peter G. Alexander, Hang Lin
Summary: In this study, hyaline cartilage-like tissues were generated from human mesenchymal stromal cells (hMSCs) and displayed robust capacity in repairing osteochondral defects in rats. The use of hMSC-generated extracellular matrix eliminated the need for exogenous scaffolds. Through optimization, it was determined that hypoxic culture and supplementation of insulin-like growth factor-1 (IGF1) in the chondrogenic medium resulted in robust cartilage formation with minimal hypertrophy. It was also demonstrated that hypoxic culture suppressed chondrogenesis and hypertrophy by modulating the Wnt/β-catenin and IGF1 pathways, respectively. This study provides a new method for generating hyaline cartilage-like tissue from hMSCs, which has potential clinical applications in cartilage tissue engineering.
ACTA BIOMATERIALIA
(2022)
Article
Oncology
Lucas Eduardo Botelho de Souza, Fernanda Ursoli Ferreira, Carolina Hassibe Thome, Heloisa Brand, Maristela Delgado Orellana, Vitor Marcel Faca, Aparecida Maria Fontes, Dimas Tadeu Covas
Summary: Melanoma cells have the capability to activate an EMT-like program and acquire metastatic traits through distinct pathways induced by MSCs' secretome, both in mouse and human cells.
Article
Cell Biology
Noreen Mumtaz, Amel Dudakovic, Asha Nair, Marijke Koedam, Johannes P. T. M. van Leeuwen, Marion P. G. Koopmans, Barry Rockx, Andre J. J. van Wijnen, Bram C. J. van der Eerden
Summary: Arboviruses like Zika virus affect bone development by targeting osteoblasts and altering bone remodeling. In this study, the researchers investigated the effects of Zika virus infection on mesenchymal stromal cells (MSCs) at different stages of osteogenesis. They found that late-stage infected MSCs showed elevated osteogenic markers, calcium content, and altered gene expression compared to early-stage infected MSCs.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Review
Chemistry, Medicinal
Fatemeh Meshkini, Nahid Ramezani-Jolfaie, Saman Sargazi, Cain C. T. Clark, Sepideh Soltani
Summary: A systematic review of the effects of lycopene on circulating IGF-1 and IGFBPs in adults found no consistent modifying effect of lycopene supplementation on IGF-1 and IGFBP levels. More research is needed to explore the effect of lycopene on the IGF-1 system.
PHYTOTHERAPY RESEARCH
(2022)
Review
Endocrinology & Metabolism
Derek LeRoith, Jeff M. P. Holly, Briony E. Forbes
Summary: The IGF family of ligands, receptors, and binding proteins play critical roles in normal human physiology and disease states. IGF-I regulates cellular growth, differentiation, and survival to control overall body growth, while IGF-II has important effects prenatally and in tissue-specific roles in adults.
MOLECULAR METABOLISM
(2021)
Article
Chemistry, Multidisciplinary
Bhavesh Premdjee, Asser S. Andersen, Mark Larance, Kilian W. Conde-Frieboes, Richard J. Payne
Summary: The text discusses the successful assembly of a 31.5 kDa phosphorylated IGFBP-2 protein using two ligation manifolds, incorporating phosphoserine post-translational modification and nine disulfide bonds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Ye Xiao, Guang-Ping Cai, Xu Feng, Yu-Jue Li, Wan-Hui Guo, Qi Guo, Yan Huang, Tian Su, Chang-Jun Li, Xiang-Hang Luo, Yong-Jun Zheng, Mi Yang
Summary: Senescence and altered differentiation potential of bone marrow stromal cells (BMSCs) lead to age-related bone loss. The splicing factor Y-box binding protein 1 (YBX1) regulates BMSC senescence and differentiation shift during aging by controlling RNA splicing. Deletion of Ybx1 in BMSCs accelerates bone loss in mice, while its overexpression stimulates bone formation. Sciadopitysin, a small compound, attenuates the degradation of YBX1 and prevents bone loss in old mice.
Article
Endocrinology & Metabolism
Anne Mette Frobert, Malene Brohus, Tinna S. Roesen, Jonas Kindberg, Ole Frobert, Cheryl A. Conover, Michael T. Overgaard
Summary: Brown bears shift from circulating ternary IGF/IGFBP/ALS complexes in the active state to binary IGF/IGFBP complexes during hibernation, indicating increased tissue IGF-bioactivity. Furthermore, brown bears use a splice variant of IGF-2, suggesting increased bone-specific targeting of IGF anabolic signaling.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Multidisciplinary Sciences
Pyunggang Kim, Jinah Park, Dong-Joon Lee, Seiya Mizuno, Masahiro Shinohara, Chang Pyo Hong, Yealeen Jeong, Rebecca Yun, Hyeyeon Park, Sujin Park, Kyung-Min Yang, Min-Jung Lee, Seung Pil Jang, Hyun-Yi Kim, Seung-Jun Lee, Sun U. Song, Kyung-Soon Park, Mikako Tanaka, Hayato Ohshima, Jin Won Cho, Fumihiro Sugiyama, Satoru Takahashi, Han-Sung Jung, Seong-Jin Kim
Summary: This study reveals the important roles of TGF-beta and Wnt signaling pathways in regulating differentiation of MSC into cartilage and bone, respectively, and the essential involvement of Mast4 as a mediator in these processes. TGF-beta inhibits Mast4 to enhance chondrogenesis of MSC by stabilizing Sox9, while Wnt stabilizes Mast4 to promote osteogenesis of MSC by facilitating β-catenin nuclear localization and Runx2 activity.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Kishor K. Sivaraj, Hyun-Woo Jeong, Backialakshmi Dharmalingam, Dagmar Zeuschner, Susanne Adams, Michael Potente, Ralf H. Adams
Summary: Bone stroma plays a crucial role in regulating osteogenesis and hematopoiesis, as well as fracture healing and disease processes. BMSCs from different bone regions, such as metaphysis and diaphysis, exhibit distinct characteristics and functions. The fate of BMSCs is controlled by signaling pathways involving PDGFR beta and transcription factor Jun-B, contributing to bone development and our understanding of BMSC lineage relationships and differentiation.
Article
Biology
Xiaoyu Li, Liang Feng, Chunmei Zhang, Jinsong Wang, Songlin Wang, Lei Hu
Summary: IGFBP7 plays a crucial role in preventing DPSCs senescence and functions by regulating the transcription of H3K36ac and p21, providing a potential target for tissue regeneration in an aging environment.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Arturo Ibanez-Fonseca, Ana Rico, Silvia Preciado, Fernando Gonzalez-Perez, Sandra Muntion, Jesus Garcia-Brinon, Maria-Carmen Garcia-Macias, Jose Carlos Rodriguez-Cabello, Miguel Pericacho, Matilde Alonso, Fermin Sanchez-Guijo
Summary: Combination of an elastin-like recombinamer (ELR)-based hydrogel with mesenchymal stromal cells (MSCs) shows potential in improving tissue reperfusion and blood vessel density in a murine hindlimb ischemia model, suggesting a promising approach for clinical application.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Immunology
Ayman F. Refaie, Batoul L. Elbassiouny, Malgorzata Kloc, Omaima M. Sabek, Sherry M. Khater, Amani M. Ismail, Rania H. Mohamed, Mohamed A. Ghoneim
Summary: MSC-based therapy for T1DM shows promise, but there are conflicting views on their immunological profile. Research focuses on understanding the mechanisms of their immunomodulatory functions and exploring ways to enhance their effects.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Diana-Alexandra Ertl, Jiajia Chen, Andreas Gleiss, Dominik Janu, Susanne Sagmeister, Adalbert Raimann, Stefan Riedl, Gabriele Haeusler
Summary: This study aimed to evaluate the relevance of serum ALS as an additional biomarker in the diagnosis of GHD, but the results showed that determination of serum ALS alone or in combination with IGF-I and IGFBP-3 did not improve the definition of biochemical GHD. The performance of IGFBP-3 was not statistically superior to ALS in short children and adolescents with suspected growth disorder.
HORMONE RESEARCH IN PAEDIATRICS
(2021)
Article
Multidisciplinary Sciences
Albert Serrano, Jessica L. Guyette, Joel B. Heim, Michael Taylor, Patrick Cherubin, Ute Krengel, Ken Teter, Suren A. Tatulian
Summary: This study found that protein disulfide isomerase (PDI) disassembles cholera toxin (CT) more efficiently, providing a possible explanation for the greater potency of CT compared to heat-labile enterotoxin (LT). Furthermore, the analysis of geometrical positioning highlighted structural differences between CT and LT, leading to distinct modes of PDI-toxin interactions.
SCIENTIFIC REPORTS
(2022)
Article
Endocrinology & Metabolism
Andre Sarmento-Cabral, Mercedes del Rio-Moreno, Mari C. Vazquez-Borrego, Mariyah Mahmood, Elena Gutierrez-Casado, Natalie Pelke, Grace Guzman, Papasani Subbaiah, Jose Cordoba-Chacon, Shoshana Yakar, Rhonda D. Kineman
Summary: The study found that knocking down GHR in adult hepatocytes leads to non-alcoholic fatty liver disease, with no significant changes observed in female mice but with symptoms of steatosis, hepatocyte ballooning, and inflammation present in male mice.
JOURNAL OF ENDOCRINOLOGY
(2021)
Article
Cell Biology
Manisha Dixit, Sher Bahadur Poudel, Shoshana Yakar
Summary: Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) play crucial roles in regulating body growth and skeletal acquisition, with their activity declining with age and leading to detrimental effects on the musculoskeletal system.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Cell Biology
Sher Bahadur Poudel, Manisha Dixit, Gozde Yildirim, Jose Cordoba-Chacon, Manuel D. Gahete, Ikeno Yuji, Thorsten Kirsch, Rhonda D. Kineman, Shoshana Yakar
Summary: The study found that adult-onset isolated GH deficiency can lead to increased severity of OA and extended lifespan in female mice. However, high levels of lymphomas were observed in both sexes with AOiGHD. Additionally, males with AOiGHD showed increased cell senescence and significantly decreased health span.
Article
Biology
Didier A. Rajon, Brian S. Canter, Calvin N. Leung, Tom A. Back, J. Christopher Fritton, Edouard I. Azzam, Roger W. Howell
Summary: The study explored the importance of direct effects and bystander effects in cancer therapy with alpha-particle emitting radiopharmaceuticals using computational modeling and Monte Carlo radiation transport simulation. Results showed that a robust bystander effect component was necessary to simulate in vivo tumor proliferation, suggesting the need for more complex models to understand the full extent of (RaCl2)-Ra-223-induced bystander effects.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2021)
Article
Oncology
Brian S. Canter, Calvin N. Leung, J. Christopher Fritton, Tom Back, Didier Rajon, Edouard Azzam, Roger W. Howell
Summary: Radiation-induced bystander effects play a role in the cytotoxicity of DTC caused by (RaCl2)-Ra-223. Both irradiated and bystander MDA-MB-231 and MCF-7 cells showed DNA damage, with MDA-MB-231 bystander cells also exhibiting increased apoptosis in (RaCl2)-Ra-223-treated animals. Additionally, irradiated osteocytes displayed increased apoptosis as well.
MOLECULAR CANCER RESEARCH
(2021)
Article
Endocrinology & Metabolism
Laris Achlaug, Lina Somri-Gannam, Shilhav Meisel-Sharon, Rive Sarfstein, Manisha Dixit, Shoshana Yakar, Mordechai Hallak, Zvi Laron, Haim Werner, Ilan Bruchim
Summary: This study evaluated the expression of ZYG11A in EOC patients and found reduced ZYG11A expression in high grade tumors, suggesting a potential tumor suppressor role. The study also identified an inverse correlation between ZYG11A and p53 levels in individual tumors. Further exploration of ZYG11A as a novel biomarker in EOC is warranted based on these findings.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Cell Biology
Rand Shibel, Rive Sarfstein, Karthik Nagaraj, Lena Lapkina-Gendler, Zvi Laron, Manisha Dixit, Shoshana Yakar, Haim Werner
Summary: Endometrial cancer is commonly linked to the insulin-like growth factor-1 (IGF1) axis, while individuals with Laron syndrome (LS) are protected from cancer development due to IGF1 deficiency. The downregulation of OR5H2 gene in LS-derived cells suggests a potential role in endometrial cancer as a target for positive regulation by IGF1.
Article
Cell Biology
Manisha Dixit, Silvana Duran-Ortiz, Godze Yildirim, Sher Bahadur Poudel, Leeann D. Louis, Andrzej Bartke, Mitchell B. Schaffler, John J. Kopchick, Shoshana Yakar
Summary: The study investigated the effects of induced somatopause on skeletal integrity using an iGHRKO mouse model, finding that induced somatopause resulted in thinner bones and compromised bone strength. There were progressive declines in osteocyte lacunar number and increases in lacunar volume, along with reductions in canalicular connectivity. Despite compromised bone morphology, osteocyte senescence was reduced in iGHRKO mice. Overall, induced somatopause compromised bone morphology and the bone marrow environment in aging mice.
Article
Cell Biology
Silvana Duran-Ortiz, Edward O. List, Yuji Ikeno, Jonathan Young, Reetobrata Basu, Stephen Bell, Todd McHugh, Kevin Funk, Samuel Mathes, Yanrong Qian, Prateek Kulkarni, Shoshana Yakar, Darlene E. Berryman, John J. Kopchick
Summary: Studies suggest that reducing growth hormone action can enhance healthy lifespan. In adult mice, disrupted GH action resulted in sexual dimorphic effects, with males showing enhanced insulin sensitivity and reduced tumors, while females exhibited increased lifespan and reduced glucose and oxidative stress.
Article
Endocrinology & Metabolism
Mark Slayton, Bijinu Balakrishnan, Abhishek Gupta, Scott Jobe, Ishika Puri, Savannah Neely, Yoshikazu Tamori, David W. Russ, Gozde Yildirim, Shoshana Yakar, Vishva M. Sharma, Vishwajeet Puri
Summary: This study identifies Fsp27 as a novel protein associated with muscle metabolism. The Fsp27-knockout model reveals that Fsp27 plays a role in muscular-fat storage, muscle endurance, and muscle strength, ultimately impacting limb movement. Additionally, the study suggests a potential metabolic paradox in which Fsp27-knockout mice, presumed to be metabolically healthy based on glucose utilization and oxidative metabolism, exhibit impaired exercise capacity and muscular performance.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Review
Cell Biology
Vicente Barrios, Julie A. Chowen, Alvaro Martin-Rivada, Santiago Guerra-Cantera, Jesus Pozo, Shoshana Yakar, Ron G. Rosenfeld, Luis A. Perez-Jurado, Juan Suarez, Jesus Argente
Summary: The GH/IGF axis is crucial in human growth, with recent research focusing on the role of the PAPP-A2 gene mutations in affecting physiology. Understanding the implications of PAPP-A2 can provide insights for controlling growth processes.
Article
Endocrinology & Metabolism
Manisha Dixit, Leeann D. Louis, Jelena Basta-Pljakic, Gozde Yildirim, Sher-Bahadur Poudel, Fancy Kumararaja, Edward O. List, Silvana Ortiz Duran, John J. Kopchick, Ryan R. Ruff, Mitchell B. Schaffler, Shoshana Yakar
Summary: Excess in growth hormone levels can have different effects on bone depending on the gender. Male mice experience bone enlargement, marrow cavity expansion, and thin cortices, while female mice have smaller bone diameter but thicker cortices and better bone quality. Excess growth hormone also leads to increased bone remodeling. In conclusion, excess growth hormone results in sexually dimorphic changes in bone structure and mass.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Pathology
Sher B. Poudel, Ryan R. Ruff, Gozde Yildirim, Manisha Dixit, Benoit Michot, Jennifer L. Gibbs, Silvana D. Ortiz, John J. Kopchick, Thorsten Kirsch, Shoshana Yakar
Summary: This study investigated the effects of long-term excess GH on the knee joint tissues. The results showed that excess GH leads to loss of articular cartilage, osteoporosis, synovitis, and chondrogenesis. The findings suggest that treatment of acromegalic arthropathy should involve inhibition of ectopic chondrogenesis and chondrocyte hypertrophy.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Geriatrics & Gerontology
Gozde Yildirim, Edmara T. P. Bergamo, Sher Bahadur Poudel, Ryan R. R. Ruff, Manisha Dixit, Bin Hu, Dindo Q. Q. Mijares, Lukasz Witek, Carolyn Chlebek, David E. E. Harrison, Randy Strong, Richard A. A. Miller, Warren Ladiges, Timothy G. G. Bromage, Clifford J. J. Rosen, Shoshana Yakar
Summary: SGLT2 inhibitors like CANA can reduce blood glucose levels, but long-term use may increase the risk of osteoporosis and cortical fractures.
Review
Endocrinology & Metabolism
Lauren Battle, Shoshana Yakar, Alessandra Carriero
Summary: Currently, there is no cure for osteogenesis imperfecta (OI) and stem cell therapy shows promise in reducing fractures in mouse models of OI. However, the efficacy of the therapy is influenced by various factors and further research is needed to establish standardized assessment criteria.
