Research Interest
Glucocorticoids are commonly used as immunosuppressants to manage a wide range of conditions, such as muscular dystrophies, rheumatoid arthritis, asthma, autoimmune diseases, organ transplantation, and even in some cancers, resulting in an estimated four million being prescribed glucocorticoids in the US. Unfortunately, glucocorticoid excess leads to harmful musculoskeletal and cardiac effects, with marked increases in fracture risks, cardiovascular diseases, and consequentially mortality rates. The Sato Laboratory investigates mechanisms by which excessive glucocorticoids induce disease in the musculoskeletal and cardiac systems with the overall goal of identifying novel targets for therapeutic intervention. We utilize in vitro, ex vivo (organ cultures), and in vivo preclinical murine models to study the pathophysiology of glucocorticoids and the musculoskeletal and cardiac responses to potential protective interventions. Currently, our research projects are focused on investigations targeting atrophy (E3 ligases), vitamin D, and canonical Wnt signaling to interfere with glucocorticoid-induced tissue loss and dysfunction.
Lab Images
Publications
- Clark A, Ghatak S, Guda PR, El Masry MS, Xuan Y, Sato AY, Bellido T, Sen CK. 2022. Myogenic tissue nanotransfection improves muscle torque recovery following volumetric muscle loss. NPJ Regenerative Medicine. 7(1):63. doi: 10.1038/s41536-022-00259-y. PubMed PMID: 36266362; PubMed Central PMCID: PMC9585072.
https://doi.org/10.1038/s41536-022-00259-y
- Sato AY, Pellegrini GG, Cregor M, McAndrews K, Choi RB, Maiz M, Johnson O, McCabe LD, McCabe GP, Ferruzzi MG, Lila MA, Peacock M, Burr DB, Nakatsu CH, Weaver CM, Bellido T. 2020. Skeletal protection and promotion of microbiome diversity by dietary boosting of the endogenous antioxidant response. J Bone Miner Res. 36(4):768-778. doi: 10.1002/jbmr.4231. Epub 2020 Dec 30. PubMed PMID: 33316081. https://doi.org/10.1002/jbmr.4231.
- Sato AY, Cregor M, McAndrews K, Li T, Condon KW, Plotkin LI, Bellido T. 2019. Glucocorticoid-induced bone fragility is prevented in female mice by blocking Pyk2/anoikis signaling. Endocrinology 160(7):1659-1673. doi: 10.1210/en.2019-00237. PubMed PMID: 31081900; PubMed Central PMCID: PMC6591015.
https://doi.org/10.1210/en.2019-00237
- Bullock WA, Hoggatt AM, Horan DJ, Elmendorf AJ, Sato AY, Bellido T, Loots GG, Pavalko FM, Robling A. 2019. Lrp4 mediates bone homeostasis and mechanotransduction through interaction with sclerostin in vivo. iScience 20:205-215. doi: 10.1016/j.isci.2019.09.023. Epub 2019 Sep 18. PubMed PMID: 31585407; PubMed Central PMCID: PMC6817631.
https://doi.org/10.1016/j.isci.2019.09.023
- Alam I, Oakes DK, Reilly AM, Billingsley C, Sbeta S, Gerard-O’Riley RL, Acton D, Sato A, Bellido T, Econs MJ. 2019. Overexpression of WNT16 does not prevent cortical bone loss due to glucocorticoid treatment in mice. JBMR Plus. 3(4):e10084. doi: 10.1002/jbm4.10084. eCollection 2019 Apr. PubMed PMID: 31044183; PubMed Central PMCID: PMC6478588.
https://doi.org/10.1002/jbm4.10084
- Sato AY, Peacock M, Bellido T. 2018. Glucocorticoid excess in bone and muscle. Clin Rev Bone Miner Metab 16(1):33-47. doi: 10.1007/s12018-018-9242-3. Epub 2018 Feb 5. PubMed PMID: 29962904; PubMed Central PMCID: PMC6022857.
10.1007/s12018-018-9242-3
- Delgado-Calle J, Hancock B, Likine EF, Sato AY, McAndrews K, Sanudo C, Bruzzaniti A, Riancho JA, Tonra JR, Bellido T. 2018. MMP14 is a novel target of PTH signaling in osteocytes that controls resorption by regulating soluble RANKL production. FASEB J. 32(5):2878-2890. doi: 10.1096/fj.201700919RRR. Epub 2018 Jan 17. PubMed PMID: 29401593; PubMed Central PMCID: PMC5901377.
https://doi.org/10.1096/fj.201700919RRR
- Sato AY, Richardson D, Cregor M, Davis HM, Au ED, McAndrews K, Zimmers TA, Organ JM, Peacock M, Plotkin LI, Bellido T. 2017. Glucocorticoids induce bone and muscle atrophy by tissue-specific mechanisms upstream of E3 ubiquitin ligases. Endocrinology 158 (3):664-677. doi: 10.1210/en.2016-1779. PubMed PMID: 28359087; PubMed Central PMCID: PMC5460781.
https://doi.org/10.1210/en.2016-1779
- Maycas M, McAndrews K, Sato AY, Pellegrini GG, Brown DM, Allen MR, Plotkin LI, Gortazar AR, Esbit P, Bellido T. 2017. PTHrP-derived peptides restore bone mass and strength in diabetic mice: additive effect of mechanical loading. J Bone Miner Res 32 (3):486-497. doi: 10.1002/jbmr.3007. Epub 2016 Oct 24. PubMed PMID: 27683064.
https://doi.org/10.1002/jbmr.3007
- Sato AY, Cregor M, Delgado-Calle J, Condon KW, Allen MR, Peacock M, Plotkin LI, Bellido T. 2016. Protection from glucocorticoid-induced osteoporosis by anti-catabolic signaling in the absence of Sost/sclerostin. J Bone Miner Res 31(1791-1802): doi: 10.1002/jbmr.2869. Epub 2016 Jun 5. PubMed PMID: 27163932; PubMed Central PMCID: PMC8499032.
https://doi.org/10.1002/jbmr.2869 - Commented in a JBMR Perspective: Baschant U, Henneicke H, Hofbauer LC, Rauner M. 2016. Sclerostin blockage—a dual mode of action after all? J Bone Miner Res 31(1787-1790): doi: 10.1002/jbmr.2988 Epub 2016 Sept 14.
- Recommendation in a F1000Prime Recommendations: Johnson, M. 2016. F1000Prime
- Recommendations of [Sato AY et al., J Bone Miner Res, 2016, 31(1791-1802)]. In F1000Prime, 13 Dec 2016; doi: 10.3410/f.726345393.793525998. F1000Prime.com/726345393#eval793525998
- Delgado-Calle J, Sato AY, Bellido T. 2017. Role and mechanism of action of sclerostin in bone. Bone 96(29-37):doi: 10.1016/j.bone.2016.10.007. Epub 2016 Oct 12. Review. PubMed PMID: 27742498; PubMed Central PMCID: PMC5328835.
https://doi.org/10.1016/j.bone.2016.10.007 - Sato AY, Tu X, McAndrews KA, Plotkin LI, Bellido T. 2015. Prevention of glucocorticoid induced-apoptosis of osteoblasts and osteocytes by protecting against endoplasmic reticulum (ER) stress in vitro and in vivo in female mice. Bone 73:60-8. doi: 10.1016/j.bone.2014.12.012. Epub 2014 Dec 19. PubMed PMID: 25532480; PubMed Central PMCID: PMC4336847.
10.1016/j.bone.2014.12.012 - Hill Gallant KM, Gallant MA, Brown DM, Sato AY, Williams JN, Burr DB. 2014. Raloxifene prevents skeletal fragility in adult female zucker diabetic sprague-dawley rats. PLoS ONE 9(9):e108262. doi: 10.1371/journal.pone.0108262. eCollection 2014. PubMed PMID: 25243714; PubMed Central PMCID: PMC4171519.
https://doi.org/10.1371/journal.pone.0108262
Funding
KL2 Mentored Research Career Development Scholar Awards
Sato (PI)
07/2022-06/2024
Translational Research Institute (TRI), Clinical and Translational Science Awards Program
“Identification of cardioprotective signatures induced by targeting MuRF1 and Vitamin D signaling in glucocorticoid-associated cardiac disease”
Goal: The goal of this project is to identify cardioprotective mechanisms and novel targets for therapeutic intervention in the context of glucocorticoid-induced cardiovascular disease.
Role: Sato (PI)
ASBMR Fund for Research and Education Grant Award
Sato (PI)
08/2018-08/2019
ASBMR
“Training in novel techniques to evaluate muscle fiber composition and metabolism”
Goal: The goal of this grant award was to receive training in new techniques to evaluate muscle fiber composition and myofiber metabolism and to optimize muscle-specific deletion of genes using tamoxifen-inducible HSA-Cre mice from Dr. K. Esser’s laboratory.
Role: Sato (PI)
T32-AR065971
Burr D (PI), Allen M, Chu G, Kacena M, Plotkin L, Wagner D
09/2015-01/2017
NIH-NIAMS
Sato PhD Thesis Defense: “Glucocorticoid-Induced Osteoporosis and Mechanisms of Intervention”
Goal: The goal of this NIAMS T32 was to prepare PhD graduate students to pursue careers in research that will ultimately improve the health of persons with musculoskeletal diseases by supporting the trainee’s research and coursework mentorship until successful completion by obtaining the PhD degree.
Role: graduate student trainee
Trainees (Five representative examples)
2021 – Seth Curl: IDeA Network of Biomedical Research Excellence Program. undergraduate student. Ouachita Baptist University. Advisor: T. Bellido. University of Arkansas for Medical Sciences.
Role: AYSato direct supervisor:
Project: Crosstalk between vitamin D receptor signaling and glucocorticoids in bone and skeletal muscle;
Training provided: unbiased identification of outliers, presentation of data, interpretation of results, scientific writing/drafting/editing, quantification of bone mineral density (BMD), lean body mass, and fat mass from dual energy x-ray absorptiometry scans, and the dissection of bone and skeletal muscle murine tissues;
Achieved: 10 min presentation and research report, awarded completion of INBRE research Program. Recommendation letters: 2023 acceptance into LSU School of Dentistry
2019 – Jennifer Shutter: Ph.D. student fall research rotation. Ph.D. graduate student. Advisor: T. Bellido. Indiana University School of Medicine.
Role: AYSato direct supervisor:
Project: Crosstalk between vitamin D receptor signaling and glucocorticoids in bone and skeletal muscle;
Training provided: presentation skills for lab meeting, quantification of osteoclast surface and number in cancellous bone of mouse lumbar vertebrae samples
Achieved: 2020 ASBMR abstract co-authorship
2018 – Whitney A. Bullock: Ph.D. graduate student. Advisor: Dr. A. Robling. Indiana University School of Medicine.
Role: AYSato direct supervisor for in vivo skeletal muscle function testing; Project: Investigating the role of Lrp4 in sclerostin mechanotransduction signaling in bone and skeletal muscle;
Training provided: interpretation of results, statistical analysis using repeated measures two-way ANOVA, in vivo assessment of skeletal muscle function using plantarflexion torque techniques;
Achieved: first author 2019 iScience manuscript publication and 2019 ASBMR oral presentation
2018 – Roy B. Choi: Ph.D. student fall research rotation. Advisor: Dr. A. Robling. Indiana University School of Medicine.
Role: AYSato direct supervisor:
Project: Investigating whether blueberry enriched diets affect the skeletal response to sex steroid deficiency depending upon sex or the expression of endogenous antioxidant response transcription factor Nrf2;
Training provided: interpretation of results, presentation skills, synthesizing cDNA, performing quantitative PCR, fundamental cell culture techniques, and mineralization Alizarin Red staining of osteoblastic OB-6 cells Achieved: 2020 JBMR manuscript and 2018 ASBMR abstract co-authorship
2017 – Troy Li: summer volunteer internship. undergraduate student. Brown University. Advisor: T. Bellido. Indiana University School of Medicine
Role: AYSato direct supervisor:
Project #1: investigating the skeletal response to excessive glucocorticoid-induced bone loss with pharmacologic inhibition of PYK2;
Project #2: investigating the role of osteocytic FAK signaling upon the anabolic skeletal effects of mechanical loading;
Training provided: statistical identification of outliers, data presentation skills, histologic quantification of apoptotic osteoblasts and osteocytes, 3-point bending mechanical testing of femoral bones, dynamic histomorphometry analysis of cancellous bone, fundamental cell culture techniques, in vitro assessment of apoptotic osteoblastic cells, analysis of dual-energy x-ray absorptiometry (DXA) for bone mineral density (BMD), and the dissection of bone and skeletal muscle murine tissues for ex vivo organ cultures
Achieved: 2019 Endocrinology manuscript and 2018 ASBMR plenary poster abstract co-authorship.
Lab Personnel
Bhawana Adhikari, Ph.D., Postdoctoral Fellow