Wei Yao, M.D.

Clinical/Research Interests

Dr. Yao received her medical degree in XianYa Medical University in China. After receiving her medical degree she trained in Internal Medicine and practiced general medicine in China. Dr. Yao obtained further research training in bone biology at the University of Utah. While at the University of Utah, Dr. Yao performed a number of studies evaluating the effect of bone active agents on bone mass and turnover in rodent models. In 2002, Dr. Yao joined the Division of Rheumatology Research Group at UCSF and her research focused on etiology and treatment of arthritis and osteoporosis. In 2004, Dr. Yao briefly joined a research group at Stanford to study the neuropeptides’ regulation in bone turnover before being recruited, in 2005, by the University of California at Davis to be an Assistant Professor of Medicine.

Dr. Yao’s research interests include:

1. One of my research focuses for the past nine years is to investigate if we would augment bone formation by targeted delivery of the mesenchymal stem cell (MSC) to bone. Specifically, we have developed a technique via specifically targeting the integrin expressed in the MSCs or osteoprogenitor cells, and then conjugate the lead compounds to alendronate (LLP2A-Ale) to make them bone specific. We have performed a number of studies to test this approach in animal models of primary osteoporosis, aging, glucocorticoid-induced bone fragility, fracture healing and in inflammatory arthritis.

Guan, M., Yao, W (co-first author, corresponding author)., Liu, R., Lam, K. S., Nolta, J., Jia, J., Panganiban, B., Meng, L., Zhou, P., Shahnazari, M., Ritchie, R. O., and Lane, N. E. (2012) Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass. Nature medicine 18, 456-462
Yao, W., Guan, M., Jia, J., Dai, W., Lay, Y. A., Amugongo, S., Liu, R., Olivos, D., Saunders, M., Lam, K. S., Nolta, J., Olvera, D., Ritchie, R. O., and Lane, N. E. (2013) Reversing bone loss by directing mesenchymal stem cells to bone. Stem cells 31, 2003-2014
Yao, W., and Lane, N. E. (2015) Targeted delivery of mesenchymal stem cells to the bone. Bone 70, 62-65

2. To invest the role of nuclear in osteoblast lineage commitment and higher peak bone mass determination. The outcome of this project could potentially lead to discovery of a bone specific progesterone receptor inhibitor that augments peak bone mass or to treat osteoporosis and sex does matters for bone (18-23).

Yao, W., Cheng, Z., Shahnazari, M., Dai, W., Johnson, M. L., and Lane, N. E. (2010) Overexpression of secreted frizzled-related protein 1 inhibits bone formation and attenuates parathyroid hormone bone anabolic effects. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 25, 190-199
Yao, W., Dai, W., Shahnazari, M., Pham, A., Chen, Z., Chen, H., Guan, M., and Lane, N. E. (2010) Inhibition of the progesterone nuclear receptor during the bone linear growth phase increases peak bone mass in female mice. PloS one 5, e11410
Collette, N. M., Genetos, D. C., Economides, A. N., Xie, L., Shahnazari, M., Yao, W., Lane, N. E., Harland, R. M., and Loots, G.G. (2012) Targeted deletion of Sost distal enhancer increases bone formation and bone mass. Proceedings of the National Academy of Sciences of the United States of America 109, 14092- 14097
Zhong, Z., Zylstra-Diegel, C. R., Schumacher, C. A., Baker, J. J., Carpenter, A. C., Rao, S., Yao, W., Guan, M., Helms, J. A., Lane, N. E., Lang, R. A., and Williams, B. O. (2012) Wntless functions in mature osteoblasts to regulate bone mass. Proceedings of the National Academy of Sciences of the United States of America 109, E2197-2204
Zhong, Z. A., Sun, W., Chen, H., Zhang, H., Lane, N. E., and Yao, W. (2015) Inactivation of the Progesterone Receptor in Mx1+ Cells Potentiates Osteogenesis in Calvaria but Not in Long Bone. PloS one 10, e0139490
Zhong, Z. A., Sun, W., Chen, H., Zhang, H., Lay, Y. E., Lane, N. E., and Yao, W. (2015) Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice. Bone 81, 614-619

3. To evaluate how the anti-resorptive agents used to prevent and treat osteoporosis influence the bone material properties including degree of bone mineralization, bone crystal size and the localized material properties of bone (7-10).
Selected publications:

Balooch, G., Yao, W., Ager, J. W., Balooch, M., Nalla, R. K., Porter, A. E., Ritchie, R. O., and Lane, N. E. (2007) The aminobisphosphonate risedronate preserves localized mineral and material properties of bone in the presence of glucocorticoids. Arthritis and rheumatism 56, 3726-3737
Yao, W., Cheng, Z., Koester, K. J., Ager, J. W., Balooch, M., Pham, A., Chefo, S., Busse, C., Ritchie, R. O., and Lane, N. E. (2007) The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength. Bone 41, 804-812
Shahnazari, M., Yao, W., Dai, W., Wang, B., Ionova-Martin, S. S., Ritchie, R. O., Heeren, D., Burghardt, A. J., Nicolella, D. P., Kimiecik, M. G., and Lane, N. E. (2010) Higher doses of bisphosphonates further improve bone mass, architecture, and strength but not the tissue material properties in aged rats. Bone 46, 1267-1274
Shahnazari, M., Yao, W., Wang, B., Panganiban, B., Ritchie, R. O., Hagar, Y., and Lane, N. E. (2011) Differential maintenance of cortical and cancellous bone strength following discontinuation of bone-active agents. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 26, 569-581

4. To understand the mechanisms for the development of glucocorticoid (GC) induced osteoporosis and bone fragility. We initiated investigations on how glucocorticoids alter cell viability via autophagy to suppress bone formation. Sustaining the level autophagy in bone formatting cells would rescue GC-induced suppression on bone formation and bone strength. We found that osteocyte autophagy plays a major role in glucocorticoid-induced “osteocytic osteolysis” and therefore decreases localized bone material properties and increases bone fragility. We have at least two potential treatment options; sclerostin-antibody and beta- ecdysone to sustain autophagy in bone forming cells and prevent GC induced bone fragility. These works have significantly expanded our knowledge of how glucocorticoids alter bone formation (11-17).

Lane, N. E., Yao, W., Balooch, M., Nalla, R. K., Balooch, G., Habelitz, S., Kinney, J. H., and Bonewald, L. F. (2006) Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 21, 466-476
Yao, W., Cheng, Z., Busse, C., Pham, A., Nakamura, M. C., and Lane, N. E. (2008) Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis: a longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice. Arthritis and rheumatism 58, 1674-1686
Yao, W., Cheng, Z., Pham, A., Busse, C., Zimmermann, E. A., Ritchie, R. O., and Lane, N. E. (2008) Glucocorticoid-induced bone loss in mice can be reversed by the actions of parathyroid hormone and risedronate on different pathways for bone formation and mineralization. Arthritis and rheumatism 58, 3485-3497
Xia, X., Kar, R., Gluhak-Heinrich, J., Yao, W., Lane, N. E., Bonewald, L. F., Biswas, S. K., Lo, W. K., and Jiang, J. X. (2010) Glucocorticoid-induced autophagy in osteocytes. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 25, 2479-2488
Jia, J., Yao, W., Guan, M., Dai, W., Shahnazari, M., Kar, R., Bonewald, L., Jiang, J. X., and Lane, N. E. (2011) Glucocorticoid dose determines osteocyte cell fate. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25, 3366-3376
Yao, W., Dai, W., Jiang, J. X., and Lane, N. E. (2013) Glucocorticoids and osteocyte autophagy. Bone 54, 279-284

Complete list of Dr. Yao’s published work in can be located at her MyNCBI Bibliography.

Title:

Associate Professor, Associate Director, Center for Musculoskeletal Health, Internal Medicine
UC Davis Medical Center
2005-Present

Education & Training:

Postdoc
Radiobiology Division
University of Utah
1997- 1999

Internal Medicine
Postgraduate
XianYa Medical University
Changsha, China
1994-1997

Resident
People’s Hospital of Beihai
Guangxi, China
1992-1994

M.D.
XianYa Medical University
Changsha, China
1987-1992

Honors and Awards:

Dean’s Team Award, Excellency in Research, UC Davis, School of Medicine, 2013
UC Davis Academic Federal Excellency in Research Award, 2012
Mentor Award, Internal Medicine, UC Davis Medical Center, 2011
ASBMR Young Investigator Award, 2003
Outstanding Young Scientist of Beihai City Award, 1997
First Degree Scholarship and the Most Outstanding Student Award, 1987-1992
Buwei-Yan Scholarship Award, Hunan Medical University, 1989-1992

Society Memberships:

American Society for Bone and Mineral Research, 1997-present
International Society of Musculoskeletal and Neuronal Interactions, 2000-present
International Chinese Hard Tissue Society, 2001-present
International Society for Stem Cells Research, 2009-present
American Society for Cell and Molecular Biology, 2011- present

Editorial Boards:

Journal of Musculoskeletal and Neuronal Interactions, 2000-Present

Select Recent Publications:

Li CY, Jee WSS, Chen JL, Mo A, Setterberg RB, Su M, Tian XY, Ling YF and Yao W. Estrogen and “exercise” have a synergistic effect in preventing bone loss in the lumbar vertebra and femoral neck of the ovariectomized rats. Calcif Tissue Int 72:42-49; 2003.

Ai M, Yao W, Li CY, Tian XY, Su M, Ling YF, Setterberg RB, Jee WSS. Bipedal stance exercise and PGE2 had synergistic effect in increasing bone mass and it lowering the PGE2 dose required to prevent ovariectomized induced cancellous bone loss in aged rats. Bone 31:402-406; 2002

Lane NE, Kumer J, Yao W, Breuning T, Wronski T, Modin G, Kinney JH. Basic fibroblast growth factor forms new trabeculae that physically connect with pre-existing trabeculae and this new bone is maintained with an anti-resorptive agent and enhanced with an anabolic agent in an osteopenic rat model. Osteoporosis Int 2003. Ma YF, Henry B, Harlan C, Hoover J, Schmidt A, Zeng QQ, Yao W, Jee WSS, Sato M. New bone formation with Teriparatide (hPTH(1-34)) is not retarded by long-term pretreatment with alendronate, estrogen or raloxifene in ovariectomized rats. Endocrinology 144:2008-2015; 2003.

Lane NE, Yao W, M Kinney JH, Modin G, Baloosh M, Wronski TJ Both hPTH (1-34) and bFGF increase trabecular bone mass in osteopenic rats, however they have different effects on trabecular bone architecture. J Bone Miner Res 18:2105-2115; 2003

Slatopolsky E, Cozzolino M, Lu Y, Finch J, Dusso A, Staniforth M, Yao W and Jee WSS Efficacy of 19-nor-1,25-(oh)2d2 in the prevention and treatment of hyperparathyroid bone disease in experimental uremia Kidney Int 63:2020-2027; 2003

Humphrey MB, Osegawara K, Yao W, Spusta S, Daw MR, Lane NE, Lanier LL, Nakamura MC Stimulation of the signaling adapter protein DAP12 during osteoclast development regulates multinucleation J Bone Miner Res 2004 19:224-234.

Buxton E, Yao W, Lane N.E. Changes in serum sRANKL, OPG and IL-6 levels in patients Glucocorticoid induced osteoporosis treated with hPTH (1-34) J Clin Endo Metab 2004 89:3332- 3336

Offley, SC, Guo TZ, Clark JD, Vogel H, Lindsey DP, Jacob CR, Yao W, Lane NE, Kingery WS. Capsaicin sensitive neurons contribute to the maintenance of cancellous bone mass, structure, and strength. J Bone Miner Res 2005; 21:257-267.

Lane NE, Yao W, Nakamura MC, Humphrey MB, , Kimmel D, Huang X, Sheppard D, Teitelbaum SL, Ross FP Mice lacking integrin β5 subunit have accelerated osteoclast maturation and increased activity in the estrogen deficient state J Bone Miner Res 2005; 20: 58-66.

Hurley M, Yao W, Lane NE. Changes in serum fibroblast growth factor 2 in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1-34). Osteoporos Int 2005 16:2080-2084.

Yao W, Hadi T, Jiang Y, Lotz J, Wronski TJ, Lane NE. Basic fibroblast growth factor improves trabecular bone connectivity and bone strength in the lumbar vertebral body of osteopenic rats. Osteoporos Int 2005 16:1939-1947.

Lane NE, Yao W, Balooch M, Krumme A, Habelitz S, Kinney JH, Bonewald LF. Glucocorticoid- treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. J Bone Miner Res 2006 21:466-476.

Kelman A, Lui L, Yao W, Krumme A, Nevitt M, Lane NE. Association of higher levels of serum cartilage oligomeric matrix protein and N-telopeptide crosslinks with the development of radiographic hip osteoarthritis in elderly women. Arthritis Rheum. 2006 Jan;54(1):236-43.

Yao W, Balooch G, Balooch M, Jiang YB, Nalla RK, Kinney J, Wronski TJ, Lane NE. Sequential treatment of ovariectomized mice with bFGF and risedronate restored trabecular bone microarchitecture and mineralization. Bone 2006 39:460-469.

Yao W, Froman CA, Cooper PA, Tian XY, Setterberg RB, Jee WSS, Lundy MW. Simvastatin did not prevent nor restore ovariectomy-induced bone loss in adult rats. J Musculoskelet Neuronal Interact. 6:277-283; 2006.

Yao W, Tian XY, Chen J, Setterberg RB, Lundy MW, Chmielzwski P, Froman CA, Jee WSS Rolipram, a phosphodiesterase 4 inhibitor, prevented cancellous and cortical bone loss by inhibiting endosteal bone resorption and maintaining periosteal bone formation in adult ovariectomized rats J Musculoskelet Neuronal Interact. 7(2):119-130; 2007.

Wu YL, Torchia J, Yao W, Lane NE, Lanier LL, Nakamura MC, Humphrey MB. Immune tyrosine-based activation motif signaling is partially bypassed during enhanced osteoclastogenesis in estrogen deficiency mouse model. PLoS ONE 7:e586; 2007.

Yao W, Su M, Zhang Q, Tian XY, Setterberg RB, Blanton C, Lundy MW, Phipps R, Jee WSS Risedronate did not block the maximal anabolic effect of PTH in aged rats. Bone 41:813-819; 2007.

Yao W, Cheng ZQ, Koester JK, Ager JW, Balooch M, Pham A, Chefo S, Busse C, Ritchie RO, Lane NE. The Degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen deficient rats and is a strong predictor of bone strength. Bone 41:804-12; 2007.

Balooch G, Yao W, Ager JW, Balooch M, Nalla RK, Porter AE, Ritchie RO, Lane NE. The aminobisphosphonate risedronate preserves localized mineral and material properties of bone in the presence of glucocorticoids. Arthritis Rheum 56 (11): 3726-3737, 2007.

Chaganti RK, Kelman A, Lui L, Yao W, Javaid MK, Bauer D, Nevitt M, Lane NE. Change in serum measurements of cartilage oligomeric matrix protein and association with the development and worsening of radiographic hip osteoarthritis. Osteoarthritis Cartilage 2007.

Johnson KA, Yao W, Lane NE, Naquet P, Terkeltaub RA. Accelerated Chondrogenesis and Up- regulated Vanin-1 Pantetheinase Activity Promote Progressive Ankylosing Intervertebral Calcification in ank/ank Mice. Am J Pathology 172(2): 440-453, 2008.

Yao W, Cheng ZQ, Busse C, Pham A, Nakamura MC, Lane NE Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis. A longitudinal study of gene expression in bone tissue from glucocorticoid treated mice. Arthritis & Rheumatism 58(6):1674-1686, 2008.

Ritchie RO, Ionova R, Koester KJ, Yao W, Lane NE, Ager III JW. Measurement of the toughness of bone: A tutorial with special reference to small animal studies. Bone 43:798-812, 2008.

Yao W, Cheng ZQ, Zimmermann ZA, Pham A, Busse C, Kinney J, Ritchie RO, Lane NE. Glucocorticoid induced bone loss can reversed with both PTH and Risedronate by different pathways of bone cell maturation and activity. Arthritis & Rheumatism 58(11):3485-3497, 2008.

You L, Temiyasathit S, Lee P, Kim CH, Tummala P, Yao W, Kingery W, Malone AM, Kwon RY, Jacobs CR. Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading. Bone 42(1):172-179, 2008.

Sabsovich I, Clark JD, Liao J, Peltz G, Lindsey DP, Jacobs CR, Yao W, Guo TZ, Kingery WS Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan Bone 42(1): 439–451, 2008.

Shahnazari M, Yao W, Corr M, Lane NE. Targeting the Wnt signaling pathway to augment bone formation. Curr Osteoporosis Rep. 6(4):142-148, 2008.

Nicolella DP, Feng JQ, Moravits DE, Bonivitch AR, Wang Y, Dusecich V, Yao W, Lane N, Bonewald LF.Effects of nanomechanical bone tissue properties on bone tissue strain: implications for osteocyte mechanotransduction. J Musculoskelet Neuronal Interact. Oct-Dec;8(4):330-1, 2008.

Cheng ZQ, Yao W, Zimmermann ZA, Busse C, Ritchie RO, Lane NE. Prolonged treatments with anti- resorptive agents and PTH have different effects on bone strength and the degree of mineralization in old estrogen deficient osteoporotic rats. JBMR 24:209-220, 2009.

Henley C, Davis J, Miller G, Shatzen E, Cattley R, Li XD, Martin D, Yao W, Lane N, Shalhoub V. The calcimimetic AMG 641 abrogates parathyroid hyperplasia, bone and vascular calcification abnormalities in uremic rats Eu J of Pharmacology 616:306-313, 2009.

Lane NE, Yao W. Developments in the scientific understanding of osteoporosis. Arthritis Research and Therapy 11 (3):228, 2009.

Yao W, Cheng ZQ, Shahnazari M, Dai WW, Johnson ML, Lane NE. Overexpression of Secreted Frizzled-Related Protein 1 inhibits bone formation and attenuates PTH bone anabolic effects. JBMR 25: 190-199, 2010.

Lane NE, Yao W. Glucocorticoid-induced bone fragility. Ann N Y Acad Sci. Mar;1192(1):81-3. 2010.

Shahnazari M, Yao W, Dai WW, Burghardt A, Ionova-Martin SS, Kimiecik M, Ritchie RO, Heeren D, Lane NE. Higher doses of bisphosphonates further improve bone mass, architecture, and strength but not the tissue material properties in aged rats. Bone 46: 1267-1274, 2010.

Finch J L, Tokumoto M, Nakamura H, Yao W, Shahnazari M, Lane N and Slatopolsky E. The effect of paricalcitol and cinacalcet on serum phosphate and bone histomorphometry in rats with chronic kidney disease. American Journal of Physiology - Renal Physiology 298: F1315-F1322, 2010.

Yao W, Dai WW, Pham A, Shahnazari M, Cheng ZQ, Chen HY, M Gaun Lane NE. Inhibition of the progesterone nuclear receptor during the bone linear growth phase increases peak bone mass in female mice. PlosOne 5:e11410, 2010.

Xia XC, Gluhak-Heinrich J, Yao W, Lane NE, Bonewald LF, Biswas SK, Lo WK, and Jiang JX. Autophagy is a Major Mechanism Attenuating the Effect of Glucocorticoid on Bone Cell Viability. JBMR 25:2479-2488, 2010.

Shahnazari M, Yao W, Dai WW, Wang B, Panganiban B, Ritchie RO,Yolanda Hagar Y, Lane NE. Differential Maintenance of Cortical and Cancellous Bone Strength following Discontinuation of Bone Active Agents JBMR 26(3):569-81, 2011.

Lane NE, Yao W. New insights into the biology of glucocorticoid-induced osteoporosis. IBMS BoneKEy. 2011 May;8(5):229-36.

Adamopoulos IE, Tessmer M, Chao CC, Adda S, Gorman D, Pierce RH, Yao W, Lane NE, Lafacee D, Bowman EP. IL-23 is critical for induction of arthritis, osteoclast formation and maintenance of bone mass. J Immunology 187:951-959, 2011.

Yao W, Jia JJ, Guan M, Dai WW, Shahnazari M, Liang J, Bonewald L, Lane NE. Glucocorticoid dose-dependently increases osteocyte autophagy. FASEB 10:3366-3376, 2011.

Yao W , Guan M, Liu RW, Jia JJ, Lam Kit, Nolta, Zhou P, Weng LP, Shahnazari M, Panganiban B, Ritchie RO, Lane NE. Directing mesenchymal stem cells to bone to increase bone formation. Nature Medicine, 18: 456–462, 2012.

Zhong ZD, Cassandra R. Zylstra-Diegel, Baker JJ, Carpenter AC, Rao S, Yao W, Guan M, Helms JA, Lane NE, Lang RA, and Williams BO. Wntless/Gpr177 Functions in Mature Osteoblasts to Regulate Bone Mass. PNAS 109(33):E2197-204; 2012.

Collette MN, Genetos D, Economides AN, Xie LQ, Yao W, Lane NE, Richard M. Harland RM, Loots GG. Targeted deletion of Sost Distal enhancer increases bone Formation and bone Mass. PNAS 109 (35):14092-7, 2012.

Yao W, Jia JJ, Amugongo S, Lay YA, Shahnazari M, Cheng ZQ, Olvera D, Ritchie RO, Addition T, Lane NE Prolonged bisphosphonate treatments had negative effects on cortical bone strength through the involvement of TGF-β1 signaling Bone 52(1):424-32, 2013.

Yao W, Dai WW, Jiang JX, Lane NE Glucocorticoids and Osteocyte Autophagy Bone 54(2):279-84, 2013.

Jia JJ, Yao W (co-first author), Amugongo S, Lay YA, Shahnazari M, Cheng ZQ, Olvera D, Ritchie RO, Addition T, Lane NE Prolonged bisphosphonate treatments had negative effects on cortical bone strength through the involvement of TGF-β1 signaling Bone 52(1): 424-32, 2013

Yao W, Dai WW, Jiang JX, Lane NE Glucocorticoids and Osteocyte Autophagy Bone 54(2): 279-84, 2013

Lane NE, Parimi N, Corr M, Yao W, Cauley JA, Nielson CM, Ix J, Laughlin G, Orwoll E. Association of Serum Fibroblast Growth Factor 23 (FGF23) and incident fractures in older men: the Osteoporotic Fractures in Men (MrOS) Study. JBMR 28(11):2325-32; 2013.

Yao W, Guan M, Jia JJ, LYa YA, Liu RW, Lam Kit, Nolta J, Olvera D, Ritchie RO, Lane NE. Reversal of bone loss induced by estrogen deficiency or aging by guiding the mesenchymal stem cells to bone. Stem Cell 31:2004-2013, 2013.

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