26932-Kitase, Yukiko
Faculty

Yukiko Kitase, DDS, PhD

Assistant Research Professor of Anatomy, Cell Biology & Physiology

Address
MS 5055
ANAT
IN
Indianapolis, IN
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Bio

I am an investigator in a program project to study the cross-talk between bone and skeletal muscle directed by Dr. Lynda Bonewald, an expert on osteocyte cell biology. One of the projects in this program focuses on muscle factors that mediate the beneficial effects of exercise on the musculoskeletal system with the goal of developing therapeutics against aging-induced osteoporosis and sarcopenia. I helped to identify the metabolite b-aminoisobutyric acid (BAIBA) as an osteocyte viability factor and conducted in vivo unloading experiments showing that BAIBA prevents bone and skeletal muscle loss. These findings were published in Cell Reports. I also found that irisin, like BAIBA, is also an osteocyte survival under oxidative stress. These results were published in Cell as a collaboration with Dr. Bruce Spiegelman. Also, as a component of the program project, I have been working on a project studying the impact of long-term exercise from middle-age to advanced age on aging-induced musculoskeletal deterioration.

I received a Ralph W. and Grace M. Showalter Research Grant in 2017 to identify the molecular mechanisms responsible for the BAIBA effects on bone, specifically, signaling mechanisms responsible for osteocyte viability and energy metabolism using in vitro and in vivo models. I have optimized a technique for cell metabolic analysis of osteocytes using a Seahorse Analyzer to examine the effect of BAIBA. These studies have led to my independent research, where I have become interested in bone energy metabolism, especially osteocyte lipid metabolism under mechanical loading. I have substantial experience in performing in vitro mechanical loading experiments, isolating primary osteocytes from young and aged mice, and generating in vitro mechanical loading data as described in this application. I have generated a PPARd osteocyte conditional knockout mouse model with start-up funds and the related in vivo and in vitro preliminary data presented in the application.

Key Publications

  1. Kitase Y, Vallejo JA, Gutheil W, Vemula H, Jähn K, Yi J, Zhou J, Brotto M, Bonewald LF. (2018) b-aminoisobutyric acid, l-BAIBA, is a muscle-derived osteocyte survival factor. Cell Rep, 22(6): 1531-1544. PMID: 29425508
  2. Kim H, Wrann CD, Jedrychowski M, Vidoni S, Kitase Y, Nagano K, Zhou C, Chou J, Parkman VA, Novick SJ, Strutzenberg TS, Pascal BD, Le PT, Brooks DJ, Roche AM, Gerber KK, Mattheis L, Chen W, Tu H, Hynes RO, Bouxsein ML, Griffin PR, Baron R, Rosen CJ, Bonewald LF, Spiegelman B M. (2018) Irisin mediates effects on bone and fat via aV integrin receptors. Cell, 175(7):1756-1768.e17. PMID: 30550785
  3. Corry KA, Zhou H, Brustovetsky T, Himes ER, Bivi N, Horn MR, Kitase Y, Wallace JM, Bellido T, Brustovetsky N, Li J. (2019) Stat3 in osteocytes mediates osteogenic response to loading. Bone Rep, 11:100218. PMID: 31440530 
  4. Prideaux M, Kitase Y, Kimble M, O'Connell TM, Bonewald LF. (2020) Taurine, an osteocyte metabolite, protects against oxidative stress-induced cell death and decreases inhibitors of the Wnt/β-catenin signaling pathway. Bone, 137:115374. PMID: 32330695
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Titles & Appointments

  • Assistant Research Professor of Anatomy, Cell Biology & Physiology
  • Education
    2000 PhD University of Tokushima
    1996 DDS University of Tokushima
  • Research

    The overall goal of my research is to understand molecular mechanisms to mediate beneficial effects of exercise to maintain the homeostasis of musculoskeletal system and to develop new or improved therapies for treating osteoporosis induced by disuse and aging. Recent studies revealed endocrine crosstalk between skeletal muscle and bone in addition to physical and mechanical interaction. In my current project, I am investigating how contracted muscle-derived factors such as b-aminoisobutyric acid (BAIBA) and irisin, affect bone metabolism as well as osteocyte viability/functions by using in vitroosteocyte cell models, conditional knockout mouse models and an in vivo disuse model. BAIBA and irisin alter energy metabolism by regulating the AMPK signaling pathway, which is involved in the regulation of autophagy and mitochondrial function. I am interested in identifying the underlying molecular mechanisms of protective effects of BAIBA and irisin on osteocyte viability and elucidating the role of AMPK signaling in osteocyte energy metabolism in physiological and pathological conditions.

  • Professional Organizations
    American Society for Bone and Mineral Research

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