Bellido Laboratory

Under the leadership of Teresita Bellido, PhD, the Bellido Laboratory investigates the mechanisms of signal transduction among and within bone cells, with particular emphasis on the biology of osteocytes. The laboratory employs in vitro, ex vivo and in vivo models to study how hormones and mechanical force act on bone cells and affect their function and life span.

Active Research

Current projects investigate the regulation of the osteocyte-derived genes by PTH; the mechanisms by which PTH, mechanical stimulation, and canonical Wnt signaling regulate bone homeostasis through actions on osteocytes; interventions that counteract the deleterious effects of glucocorticoid excess on bone and muscle; and the role of osteocytes in multiple myeloma musculoskeletal disease.

Collaborative projects investigate the role of the transcription factor Nrf2 in the protection of the skeleton induced by berry diets; the function of connexin43 in bone; the role of estrogen receptor beta in osteocytes for mechanobiology; and the regulation of cartilage function by PTH receptor signaling. The laboratory receives funding from the NIH, VA and the biopharma industry.

As Principal Investigator (PI) or Project Leader

10/1/2016-9/31/2019 PharmaMar S.A. Characterization of Aplidin® (plitidepsin) effects on multiple myeloma (MM)-induced bone disease. Role: PI

9/30/2014-8/31/2019 NIH-NCCAM R01-AT008754 and O2S1-AT008754. Berries and bone. Role: PI of subcontract IU-Purdue University; PI C Weaver

04/2017-03/2022 NIH R01 CA209882. Contribution of Osteocytes to the Musculoskeletal Effects of Multiple Myeloma. Role MPI with GD Roodman

4/1/2018-3/30/2022 VA I01 BX002104-05 Merit Award. PTH receptor Signaling and Diabetes-induced Bone Disease. Role: PI

9/01/2011-5/31/2023 NIH R01 2R01AR059357-06. Glucocorticoid-induced Atrophy in Bone and Muscle Role: PI

As co-Investigator, Mentor or Collaborator

8/20/2018-7/31/2020 NIH-NIAMS R21AR074012-01. Nrf2 activation for treatment of osteoporosis. Role: Consultant; PI J Li

5/15/2018-4/30/2020 NIH-NIAMS R21AR071559-01. Mechanisms of Osteocyte Mechanotransduction in Dynamic Bone Adaptation. Role: PI of subcontract IU-University of Pensylvania; PI J Boerckel

12/1/15-11/30/2020 NIH R01 AR068332. CaMKK2 Inhibition as a Dual-Action Bone Anabolic and Anti-Catabolic Therapy in Osteoporosis. Role: Co-Investigator. PI: U Sankar.

4/1/2015-3/31/2020 NIH R01AR067210. Osteocyte apoptosis and regulation of bone resorption with aging. Role: Co-Investigator. PI: LI Plotkin

12/1/2011-11/31/2020 VA I01 BX001478 Merit Award. Harnessing the anabolic potential of Wnt signaling to improve bone health. Role Co-I. PI: AR Robling

Recent Publications

Kegelman CD, Mason DE, Dawahare JH, Horan D, Vigil GD, Howard SS, Robling AR, Bellido T, Boerckel JD. Skeletal cell YAP and TAZ combinatorially promote bone development. FASEB Journal (in press) 26Apr2018 https://doi.org/10.1096/fj.201700872R

Delgado-Calle J, Hancock B, Likine EF, Sato AY, McAndrews K, Sanudo C, Bruzzaniti A, Riancho JA, Tonra JR, Bellido T. MMP14 is a novel target of PTH signaling in osteocytes that controls resorption by regulating soluble RANKL production. FASEB Journal (in press) 26 Apr 2018 https://doi.org/10.1096/fj.201700919RRR

Davis HM, Aref MW, Aguilar-Perez A, Pacheco-Costa R, Allen K, Valdez S, Herrera C, Atkinson EG, Mohammad A, Lopez D, Harris MA, Harris SE, Allen MR, Bellido T, Plotkin LI. Cx43 overexpression in osteocytes prevents osteocyte apoptosis and preserves cortical bone quality in aging mice. Journal of Bone and Mineral Research-Plus DOI:10.1002/jbm4.10035 (in press).

Alam I, Oakes D, Reilly A, Billingsley C, Sbeta S, Gerard-O’Riley R, Acton D, Sato AY, Bellido T, Econs M. Overexpression of WNT16 does not rescue cortical bone loss due to glucocorticoid treatment in mice. Journal of Bone and Mineral Research-Plus DOI: 10.1002/jbm4.10084 (in press).

Li J-Y, Yu M, Tyagi AM, Vaccaro C, Hsu E, Adams J, Bellido T, Weitzmann MN, Pacifici R. IL-17 receptor signaling in osteoblastic/osteocytes mediates PTH-induced bone loss and enhances osteocytic RANKL production. Journal of Bone and Mineral Research. 2018 DOI: 10.1002/jbmr.3600 (in press). 30399207

Rauner M, Baschant U, Roetto A, Pellegrino RM, Salbach-Hirsch J, Weidner H, Rother S, Hintze V, Campbel G, Petzold A, Lemaitre R, Henry I, Bellido T, Theurl I, Altamura S, Muckenthaler MU, Schett G, Komla Ebri D, Bassett DJH, Williams GR, Platzbecker U, Hofbauer LC. Transferrin receptor 2 is a novel BMP receptor that regulates bone formation and ossification. Nature Metabolism, (in press).

Wu Y, Yuan X, Perez KC, Hyman S, Wang L, Pellegrini G, Salmon B, Bellido T, Helms JA. Aberrantly elevated Wnt signaling is responsible for cementum overgrowth and dental ankylosis. Bone, 2018 Oct 25. pii: S8756-3282(18)30403-4. doi: 10.1016/j.bone.2018.10.023. [Epub ahead of print]

Maycas M, McAndrews KA, Sato AY, Pellegrini GG, Brown DM, Allen MR, Plotkin LI, Gortazar AR, Esbrit P, Bellido T. PTHrP-Derived Peptides Restore Bone Mass and Strength in Diabetic Mice: Additive Effect of Mechanical Loading. Journal of Bone and Mineral Research 2017 Mar;32(3):486-497. doi: 10.1002/jbmr.3007. Epub 2016 Oct 24.

Delgado-Calle J, Tu X, Pacheco-Costa R, McAndrews K, Edwards R, Pellegrini G, Kuhlenschmidt K, Olivos N, Robling A, Peacock M, Plotkin LI, Bellido T. Control of Bone Anabolism in Response to Mechanical Loading and PTH by Distinct Mechanisms Downstream of the PTH Receptor. Journal of Bone and Mineral Research, 2017 Mar;32(3):522-535. doi: 10.1002/jbmr.3011. Epub 2016 Oct 27.

Davis HM, Pacheco-Costa R, Atkinson EG, Brun LR, Gortazar AR, Harris J, Hiasa M, Bolarinwa SA, Yoneda T, Ivan M, Bruzzaniti A, Bellido T, Plotkin LI. Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging. Aging Cell (2017). doi: 10.1111/acel.12586

Komaba H, Kaludjerovic J, Hu DJ, Nagano K, K Amano, Ide N, Sato T, Densmore MJ, Hanai J, Olauson H, Bellido T, Larsson TE, Baron R, Lanske B. Klotho in osteocytes regulates bone formation: the role in bone physiology and renal osteodystrophy. Kidney International 2017 Apr 8. pii: S0085-2538(17)30120-5. doi: 10.1016/j.kint.2017.02.014.

Long F, He G, Shi Y, Lim J, Bellido T, Ni J. Differential involvement of Wnt signaling in Bmp regulation of cancellous versus periosteal bone growth. Bone Research 2017 Jun 6;5:17016. doi: 10.1038/boneres. 2017.16.

Delgado-Calle J, Anderson J, Cregor MD, Hiasa M, Chirgwin JM, Carlesso N, Yoneda T, Mohammad KS, Plotkin LI, Roodman GD, Bellido T. Bidirectional Notch signaling and osteocyte-derived factors drive tumor cell proliferation and bone destruction in multiple myeloma. Cancer Research, 2016, DOI: 10.1158/0008-5472.CAN-15-1703.

Sato AY, Cregor M, Delgado-Calle J, Condon KW, Allen MR, Peacock M, Plotkin LI, Bellido T. Protection from Glucocorticoid-Induced Osteoporosis by Anti-Catabolic Signaling in the Absence of Sost/Sclerostin. Journal of Bone and Mineral Research, 31(10): 1791-1802, 2016

Pellegrini GG, Morales CC, Wallace TC, Plotkin LI, Bellido T. Avenanthramides prevent osteoblast and osteocyte apoptosis and induce osteoclast apoptosis in an Nrf2-independent manner. Nutrients, 2016 8, 423-427; doi:10.3390/nu8070423

Maycas M, McAndrews KA, Sato AY, Pellegrini GG, Brown DM, Allen MR, Plotkin LI, Gortazar AR, Esbrit P, Bellido T. PTHrP-Derived Peptides Restore Bone Mass and Strength in Diabetic Mice: Additive Effect of Mechanical Loading. Journal of Bone and Mineral Research doi 0.1002/jbmr.3007, 2016.

Delgado-Calle J, Tu X, Pacheco-Costa R, McAndrews K, Edwards R, Pellegrini G, Kuhlenschmidt K, Olivos N, Robling A, Peacock M, Plotkin LI, Bellido T. Control of Bone Anabolism in Response to Mechanical Loading and PTH by Distinct Mechanisms Downstream of the PTH Receptor. Journal of Bone and Mineral Research doi: 10.1002/jbmr.3011, 2016.

Sato AY, Tu X, McAndrews KA, Plotkin LI, Bellido T. 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: 60-68, 2015

Tu X,* Delgado-Calle J,* Condon K, Maycas M, Zhang H, Carlesso N, Taketo MM, Burr D, Plotkin LI, Bellido T. Osteocytes mediate the anabolic actions of canonical Wnt/βcatenin signaling in bone. Proceedings of National Academy of Sciences, 112 (5) E478-E486, 2015. [Epub ahead of print] (Highlighted in Nature Reviews Endocrinology; and in Nature Reviews Rheumatology) *Both first authors

Bellido Lab News

AAOMM/SAO Holds ASBMR Highlights Session in Argentina http://www.asbmr.org/publications/news/newsdetail.aspx?cid=35a92e5b-03aa-41e5-8c9c-b8abf29c1d42#.XBvmAPZFyUk

Join Us in Congratulating the 2018 Election Winners! http://www.asbmr.org/publications/news/newsdetail.aspx?cid=c7e2d680-3a9b-4659-ae73-861ad0fc8b95#.XBvvEPZFyUk

Congratulations to the 2018 Recipients of the Fund for Research and Education Research Grants! http://www.asbmr.org/publications/news/newsdetail.aspx?cid=5fcccf15-5326-4699-995f-498dd3b31aea#.XBvvPvZFyUk

2018 ASBMR Gideon A. Rodan Excellence in Mentorship Award http://www.asbmr.org/meetings/asbmrawards/detail.aspx?cid=c24c7d1c-f03d-443e-a805-9126dfc88f06

Interview with Teresita Bellido, PhD, ASBMR President Elect in ENDOWEB https://www.endoweb.net/index.php/es/19-endo-global/entrevistas/575-entrevista-a-teresita-bellido

Research Team

Teresita M. Bellido, PhD

Teresita M. Bellido, PhD

Professor of Anatomy & Cell Biology

Additional Research Team Members

Postdoctoral Fellows

Amy Y. Sato, PhD
S. Serra Ucer Ozgurel

Graduate Students

Emily Atkinson

Technical Assistants

Kevin McAndrews
Melony Cregor
David Halladay

Collaborators

Jesus Delgado-Calle
G. David Roodman
C. Weaver
A. Robling
J. Li
J. Boerckel