Bonewald Lab

The research lab of Lynda Bonewald, PhD, focuses on the biology and function of the osteocyte.

Investigators in this lab have two major focus areas: the crosstalk between osteocyte and muscle and the role of the osteocyte in calcium homeostasis under calcium demanding conditions.

Active Research

Osteocyte Regulation of Bone Muscle with Age

Muscle secretes factors that maintain osteocyte viability and function, and conversely osteocytes produce factors that support myogenesis and muscle function. These factors are being identified and their functions characterized.

Extracellular Vesicle Mediated Cell-Cell Communication in Bone

The lab is exploring the role of the osteocyte in calcium homeostasis under calcium demanding conditions such as during pregnancy. The mechanisms by which osteocytes can remove and replace calcium in their microenvironment is being examined. Trainees can learn osteocyte and muscle cell culture, isolation of primary osteocytes and muscle satellite cells, muscle contractility, application of fluid flow shear stress, mitochondrial imaging, loading and unloading of transgenic animals, in addition to standard molecular approaches and analyses.

Osteocyte Regulation of Bone Muscle with Age- Core A: Administrative Core and Subproject I: Muscle Regulation of Osteoblast/Osteocyte Function in Young compared with Aged Animals. Extracellular Vesicle Mediated Cell-Cell Communication in Bone.

  • Thiagarajan G, Begonia M, Dallas M, Lara N, Johnson M. Determination of Elastic Modulus in Mouse Bones Using a Nondestructive Microindentation Technique using Reference Point Indentation. Journal of Biomechanical Engineering 140: (11 pages) 2018. PMCID: PMC6056200
  • Kitase Y, Vallejo JA, Gutheil W, Vemula H, Jähn K, Yi J, Zhou J, Brotto M, Bonewald LF. b-aminoisobutyric Acid, L-BAIBA, Is a Muscle-Derived Osteocyte Survival Factor.Cell Rep. 2018 Feb 6;22(6):1531-1544. PMID: 29425508; PMCID: PMC5832359
  • Hyeonwoo Kim, Christiane D. Wrann, Mark Jedrychowski, Sara Vidoni, Yukiko Kitase, Kenichi Nagano, Chenhe Zhou, Joshua Chou, Virginia-Jeni A. Parkman, Scott J. Novick, Timothy S. Strutzenberg, Bruce D. Pascal, Phuong T. Le, Daniel J. Brooks, Alexander M. Roche, Kaitlyn K. Gerber, Laura Mattheis, Wenjing Chen, Hua Tu, Richard O. Hynes, Mary L. Bouxsein, Patrick R. Griffin, Roland Baron, Clifford J. Rosen, Lynda F. Bonewald, and Bruce M. Spiegelman. Irisin Mediates Effects on Bone and Fat via alphaV Integrin Receptors Cell 175: 1756-1768 2018 PMID: 30550785
  • Lu, Y, Kamel-El Sayed SA, Grillo MA, Veno PA, Dusevich V, Tiede-Lewis LM, Phillips CL, Bonewald LF, Dallas SL. (2018) Live Imaging of Type I Collagen Assembly Dynamics in Cells Stably Expressing GFP-Collagen Constructs. J. Bone Miner. Res. 33(6):1166-1182. PMID: 29461659
  • Avin KG, Vallejo JA, Chen NX, Wang K, Touchberry CD, Brotto M, Dallas SL, Moe SM, Wacker MJ. Fibroblast Growth Factor 23 Does Not Directly Influence Skeletal Muscle Cell Proliferation and Differentiation or Ex Vivo Contractility (2018). Am J Physiol Endocrinol Metab. 315(4):E594-E604.. PMID: 29558205; PMCID: PMC6230710
  • Lu, Y, Kamel-El Sayed SA, Grillo MA, Veno PA, Dusevich V, Tiede-Lewis LM, Phillips CL, Bonewald LF, Dallas SL. (2018) Live Imaging of Type I Collagen Assembly Dynamics in Cells Stably Expressing GFP-Collagen Constructs. J. Bone Miner. Res. 33(6):1166-1182. PMID: 29461659; PMCID: PMC6425932
  • Maurel DB, Matsumoto T, Vallejo J, Johnson MR, Brotto M, Dallas SL, Harris MA, Harris SE, Bonewald LF (2019). Characterization of a novel murine Sost ERT2 Cre model targeting osteocytes. Bone Research 7:6. PMID: 30820362; PMCID: PMC6382861
  • Tiede-Lewis LM and Dallas, SL (2019). Changes in the Osteocyte Lacunocanalicular Network with Aging. BONE: 122:101-113. [Special issue on musculoskeletal aging]. PMID: 30743014; PMCID: PMC6638547
  • Huang J, Wang K, Shiflett LA, Brotto L, Bonewald LF, Wacker MJ, Dallas SL, Brotto M. Fibroblast growth factor 9 (FGF9) inhibits myogenic differentiation of C2C12 and human muscle cells. Cell Cycle. 2019 Dec;18(24):3562-3580. doi:10.1080/15384101.2019.1691796. PMCID: PMC6927711
  • Mo C, Wang Z, Bonewald L, Brotto M. “Multi-Staged Regulation of Lipid Signaling Mediators during Myogenesis by COX-1/2 Pathways”. Int J Mol Sci. 2019 Sep 4;20(18). pii: E4326. PMCID: PMC6769623
  • Wang, K, Le L, Chun B, Tiede-Lewis LM, Shiflett LA, Prideaux M, Campos RS, Veno PA, Xie Y, Dusevich V, Bonewald LF, Dallas SL (2019). A Novel Osteogenic Cell Line Expressing a Membrane-Targeted GFP in Osteocytes Forms 3D Bone-like Structures that Mimic the Lacunocanalicular Structure of in vivo Bone. J Bone Miner Res. 2019 34(6): 979-995. PMID: 30882939; PMCID: PMC7350928
  • Shiflett LA, Tiede-Lewis LM, Xie Y, Lu Y, Ray EC, Dallas SL (2019). Collagen Dynamics during the Process of Osteocyte Embedding and Mineralization. Front Cell Dev Biol.18;7:178. PMID: 31620436; PMCID: PMC6759523
  • Wang Z, Bian L, Mo C, Shen H, Zhao LJ, Su KJ, Kukula M, Lee JT, Armstrong DW, Recker R Lappe J, Bonewald LF, Deng HW, Brotto M. “Quantification of aminobutyric acids and their clinical applications as biomarkers for osteoporosis”. Nature Commun Biol. 2020 Jan 22;3(1):39. PMCID: PMC6976694
  • Kola, S., Begonia, M. T., Tiede-Lewis, L., Laughrey, L., Dallas, S., Johnson, M. L., & Thiagarajan, G. Osteocyte Lacunar Strain Determination Using Multiscale Finite Element Analysis. Bone Reports. 2020 May 19;12:100277. doi: 10.1016/j.bonr.2020.100277. eCollection 2020 Jun. PMID: 32478144, PMCID: PMC7251370
  • Dallas SL and Moore DS (2020). Using Confocal Imaging Approaches to Understand the Structure and Function of Osteocytes and the Lacunocanalicular Network. Bone: 138:115463. PMID: 32512167; PMCID: PMC7423610
  • Thiagarajan G., Laughrey, L. E., Niroobakhsh, M., & Lara-Castillo, N. (2020). Multiscale finite element modeling of mechanical strains and fluid flow in osteocyte lacunocanalicular system. Bone, 115328. doi:10.1016/j.bone.2020.115328 PMID: 32201360; PMCID: PMC7354216
  • Oakley CI, Vallejo JA, Wang D, Gray M, Tiede-Lewis LM, Shawgo T, Daon E, Zorn G, Stubbs JR, Wacker MJ. Trimethylamine-N-Oxide acutely increases cardiac muscle contractility. American Journal of Physiology: Heart and Circulatory Physiology. 318: H1272-H1282, 2020. PMID: 32243768; PMCID: PMC7346532
  • Wang H, Li T, Wang X, Yin X, Zhao N, Zou S, Duan P, Bonewald LF. The role of sphingosine-1-phosphate signaling pathway in cementocyte mechanotransduction. Biochem BIophys Res Commun 2020 PMID 31941604
  • Prideaux M, Kitase Y, Kimble M, O’Connell TM, Bonewald LF. Taurine, an osteocyte metabolite, protects against oxidative stress-induced cell death and decreases inhibitors of the Wnt/b-catenin signaling pathway Bone 2020 PMID: 32330695; PMCID: PMC7369146
  • Biguetti CC, Couto MCR, Silva ACR, Shindo JVTC, Rosa VM, Shinohara AL, Andreo JC, Duarte MAH, Wang Z, Brotto M, Matsumoto MA. New Surgical Model for Bone-Muscle Injury Reveals Age and Gender-Related Healing Patterns in the 5 Lipoxygenase (5LO) Knockout Mouse. Front Endocrinol (Lausanne). 2020 Aug 11;11:484. doi: 10.3389/fendo.2020.00484. PMCID: PMC7431610
  • Mumtaz, H, Lara-Castillo N, Scott J, Begonia M, Dallas, M, Johnson ML, Thiagarajan G, Age and Gender Related differences in Load-Strain response in C57Bl/6 mice. Aging (Albany NY). 2020 Dec 17;12(24):24721-24733. doi: 10.18632/aging.202350. PMID: 33346747; PMCID: PMC7803533
  • Mumtaz, H, Dallas, M, Begonia M, Lara-Castillo N, Scott J, Johnson ML, Thiagarajan G, Age-related and sex-specific effects on architectural properties and biomechanical response of the C57BL/6N mouse femur, tibia and ulna. Bone Rep. 2020 Apr 23;12:100266. doi: 10.1016/j.bonr.2020.100266. eCollection 2020 Jun. PMID: 32420415; PMCID: PMC7215114
  • Lara-Castillo N and Johnson ML Bone-Muscle Mutual Interactions Curr Osteoporos Rep. 2020 Aug;18(4):408-421. doi: 10.1007/s11914-020-00602-6. PMID: 32519283; PMCID: PMC8059358
  • Shochat C, Wang Z, Mo C, Nelson S, Donaka R, Huang J, Karasik D, Brotto M. Deletion of SREBF1, a Functional Bone-Muscle Pleiotropic Gene, Alters Bone Density and Lipid Signaling in Zebrafish. 2021 Jan 1;162(1): bqaa189. doi: 10.1210/endocr/bqaa189. PMCID: PMC7745669
  • Awad K, Ahuja N, Fiedler M, Peper S, Wang Z, Aswath P, Brotto M, Varanasi V. Ionic Silicon Protects Oxidative Damage and Promotes Skeletal Muscle Cell Regeneration. Int J Mol Sci. 2021 Jan 6;22(2):497. doi: 10.3390/ijms22020497. PMCID: PMC7825403
  • Kojouharov HV, Chen-Charpentier BM, Solis FJ, and Brotto M. A simple model of immune and muscle cell crosstalk during muscle regeneration. Math Biosci. 2021 Mar;333:108543. doi: 0.1016/j.mbs.2021.108543. Epub 2021 Feb 16. PMCID: PMC8753861
  • Mo C, Du Y, O’Connell T. Applications of Lipidomics to Age-Related Musculoskeletal Disorders. Curr Osteoporos Rep. DOI: 10.1007/s11914-021-00656-0. PMCID: PMC8016815
  • Gong R, Xiao HM, Zhang YH, Zhao Q, Su KJ, Lin X, Mo CL, Zhang Q, Du YT, Lyu FY, Chen YC, Peng C, Liu HM, Hu SD, Pan DY, Chen Z, Li ZF, Zhou R, Wang XF, Lu JM, Ao ZX, Song YQ, Weng CY, Tian Q, Schiller MR, Papasian CJ, Brotto M, Shen H, Shen J, Deng HW. Identification and Functional Characterization of Metabolites for Bone Mass in Peri-/Post-menopausal Chinese Women. J Clin Endocrinol Metab. 2021 Mar 8:dga b146. doi: 10.1210/clinem/dgab146. Epub ahead of print. PMID: 33693744; PMCID: PMC8277206
  • Ito N, Prideaux M, Wijenayaka AB, Yang D, Ormsby RT, Bonewald LF, Atkins GJ “Sclerostin directly stimulates osteocyte synthesis of Fibroblast Growth Factor 23” Cal Tiss Int. 2021 PMID: 33616712
  • Pin F, Prideaux M, Huot JR, Essex AL, Plotkin LI, Bonetto A, Bonewald LF “Non-bone metastatic cancers promote osteocyte-induced bone destruction” Cancer Lett 2021 PMIC: 34233150. PMCID: PMC8440379
  • Nakamura MT, Zhang H, Guo D, Ueharu H, Pan H, Scott G, Harris M, Ray M, Feng JQ, Harris SE, Bonewald LF, Mishina Y “Podoplanin is dispensable for mineralized tissue formation and maintenance in the Swiss outbred mouse background”. genesis The Journal of Genetics and Development. 2021,
  • Pin F, Jones AJ, Huot, JR, Narasimhan A, Zimmers TA, Bonewald, LF, Bonetto, A. “RANKL Blockade reduced cachexia and bone loss induced by non-metastatic ovarian cancer in mice”. JBMR 2021 PMID 34904285; PMCID: PMC8940654
  • Jackson, E., Lara-Castillo, N., Akhter, M.P., Dallas, M. Scott, J.M., Ganesh, T. and Johnson, M.L.: “Osteocyte Wnt/β-catenin pathway activation upon mechanical loading is altered in ovariectomized mice” Bone Rep. 2021 Sep 14;15:101129. doi: 10.1016/j.bonr.2021.101129. eCollection 2021 Dec. PMCID: PMC8455641
  • Westendorf JJ, Bonewald LF, Kiel DP, Burtt NP. The Musculoskeletal Knowledge Portal: improving access to multi-omics data. Nat Rev Rheumatol. 2022 Jan;18(1):1-2. doi: 10.1038/s41584-021-00711-1. PMID: 34686856; PMCID: PMC9346538.

  • Glorieux FH, Bonewald LF, Harvey NC, van der Meulen MCH. Potential influences on optimizing long-term musculoskeletal health in children and adolescents with X-linked hypophosphatemia (XLH). Orphanet J Rare Dis. 2022 Jan 31;17(1):30. doi: 10.1186/s13023-021-02156-x. PMID: 35101067; PMCID: PMC8802511.

  • Yoshimoto T, Kittaka M, Doan AAP, Urata R, Prideaux M, Rojas RE, Harding CV, Henry Boom W, Bonewald LF, Greenfield EM, Ueki Y. Osteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection. Nat Commun. 2022 Nov 4;13(1):6648. doi: 10.1038/s41467-022-34352-z. PMID: 36333322; PMCID: PMC9636212.

  • Pin F, Jones AJ, Huot JR, Narasimhan A, Zimmers TA, Bonewald LF, Bonetto A. RANKL Blockade Reduces Cachexia and Bone Loss Induced by Non-Metastatic Ovarian Cancer in Mice. J Bone Miner Res. 2022 Mar;37(3):381-396. doi: 10.1002/jbmr.4480. Epub 2021 Dec 13. PMID: 34904285; PMCID: PMC8940654.

  • Li T, Wang H, Jiang Y, Guan Y, Chen S, Wu Z, Zou S, Bonewald LF, Duan P. Canonical Wnt/β-catenin signaling has positive effects on osteogenesis, but can have negative effects on cementogenesis. J Periodontol. 2022 Nov;93(11):1725-1737. doi: 10.1002/JPER.21-0599. Epub 2022 Aug 10. PMID: 35642884.

For a full list of Dr. Bonewald’s publication history, please find her on Google Scholar or PubMed 

Faculty Research Team

Lynda F. Bonewald, PhD

Director, Indiana Center for Musculoskeletal Health

Yukiko Kitase, DDS, PhD

Assistant Research Professor of Anatomy, Cell Biology & Physiology

Charalampos Lyssikatos, MD

Assistant Research Professor of Orthopaedic Surgery

Fabrizio Pin, PhD

Assistant Professor of Anatomy, Cell Biology & Physiology