Amy Lynn McNulty

Bio

The McNulty Lab is working to develop strategies to prevent osteoarthritis and to promote tissue repair and regeneration following joint injury. In order to accomplish this, we are working in three main areas.  1) We are working to understand the pathways that are activated by normal and injurious mechanical loading of cartilage and meniscus and how these mechanotransduction pathways are altered during aging, injury, and tissue degeneration. A greater understanding of alterations in mechanosensitive signaling mechanisms with aging and injury will likely reveal potential targets to promote tissue repair and prevent tissue degeneration and osteoarthritis development. 2) We are developing meniscus tissue engineered constructs that will be utilized to repair and replace meniscus tissue lost due to injury and surgical resection.  3)  We are focusing on the biological and biomechanical changes that occur in the joint following meniscus injury and how these may contribute to osteoarthritis development.   

Education

• Ph.D. Duke University, 2005

Positions

• Associate Professor in Orthopaedic Surgery
• Associate Research Professor of Cell Biology
• Associate Professor of Biomedical Engineering
• Associate Professor in the Department of Pathology
• Affiliate of the Duke Regeneration Center

Courses Taught

• PATHOL 793: Research Independent Study
• BME 792: Continuation of Graduate Independent Study
• BME 791: Graduate Independent Study

Publications

• Libke ML, Cunningham DJ, Furman BD, Yi JS, Brunger JM, Kraus VB, et al. Mode of injury and level of synovitis alter inflammatory chondrocyte gene expression and associated pathways. Sci Rep. 2024 Nov 21;14(1):28917.
• Fei K, Andress BD, Kelly AM, Chasse DAD, McNulty AL. Meniscus gene expression profiling of inner and outer zone meniscus tissue compared to cartilage and passaged monolayer meniscus cells. Sci Rep. 2024 Nov 9;14(1):27423.
• Pawar A, Anderson B, Pourdeyhimi B, McNulty AL, Fisher M, Shirwaiker R. 3D melt blowing of Elastollan thermoplastic polyurethane for tissue engineering applications: A pilot study. Manufacturing Letters. 2024 Oct 1;41:357–63.
• Betsch K, Martinez VG, Lyons LP, Weinberg JB, Wittstein JR, McNulty AL. Shedding light on the effects of blood on meniscus tissue: the role of mononuclear leukocytes in mediating meniscus catabolism. Osteoarthritis Cartilage. 2024 Aug;32(8):938–49.
• Zhao Q, Holt A, Spritzer CE, DeFrate LE, McNulty AL, Wang N. High angular resolution diffusion imaging (HARDI) of porcine menisci: a comparison of diffusion tensor imaging and generalized q-sampling imaging. Quant Imaging Med Surg. 2024 Apr 3;14(4):2738–46.
• Firoozi S, Ley JC, Chasse DAD, Attarian DE, Wellman SS, Amendola A, et al. Healthy but not osteoarthritic human meniscus-derived matrix scaffolds promote meniscus repair. Front Bioeng Biotechnol. 2024;12:1495015.
• Coppock JA, McNulty AL, Porter Starr KN, Holt AG, Borack MS, Kosinski AS, et al. The effects of a 6-month weight loss intervention on physical function and serum biomarkers in older adults with and without osteoarthritis. Osteoarthr Cartil Open. 2023 Sep;5(3):100376.
• Andress B, Hoffman M, McNulty AL. Analytical validation and quality control/quality assurance practices for improved rigor and reproducibility of biochemical assays in orthopaedic research. J Orthop Res. 2023 Jul;41(7):1618–23.
• Bradley PX, Thomas KN, Kratzer AL, Robinson AC, Wittstein JR, DeFrate LE, et al. The Interplay of Biomechanical and Biological Changes Following Meniscus Injury. Curr Rheumatol Rep. 2023 Feb;25(2):35–46.
• Buchanan MW, Furman BD, McNulty AL, Olson SA. Combination of Lidocaine and IL-1Ra Is Effective at Reducing Degradation of Porcine Cartilage Explants. Am J Sports Med. 2022 Jun;50(7):1997–2006.
• Andress BD, Irwin RM, Puranam I, Hoffman BD, McNulty AL. A Tale of Two Loads: Modulation of IL-1 Induced Inflammatory Responses of Meniscal Cells in Two Models of Dynamic Physiologic Loading. Front Bioeng Biotechnol. 2022;10:837619.
• Cutcliffe HC, Kottamasu PK, McNulty AL, Goode AP, Spritzer CE, DeFrate LE. Mechanical metrics may show improved ability to predict osteoarthritis compared to T1rho mapping. J Biomech. 2021 Dec 2;129:110771.
• Arrigoni P, Ruprecht JC, Chasse DAD, Glass KA, Andress B, Guilak F, et al. Optimization of Meniscus Cell Transduction Using Lentivirus and Adeno-Associated Virus for Gene Editing and Tissue Engineering Applications. Cartilage. 2021 Dec;13(2_suppl):1602S-1607S.
• Kim-Wang SY, Holt AG, McGowan AM, Danyluk ST, Goode AP, Lau BC, et al. Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries. Arthritis research & therapy. 2021 Nov;23(1):280.
• Andress B, Kim JH, Cutcliffe HC, Amendola A, Goode AP, Varghese S, et al. Meniscus cell regional phenotypes: Dedifferentiation and reversal by biomaterial embedding. J Orthop Res. 2021 Oct;39(10):2177–86.
• Lyons LP, Weinberg JB, Wittstein JR, McNulty AL. Blood in the joint: effects of hemarthrosis on meniscus health and repair techniques. Osteoarthritis Cartilage. 2021 Apr;29(4):471–9.
• Lee W, Nims RJ, Savadipour A, Zhang Q, Leddy HA, Liu F, et al. Inflammatory signaling sensitizes Piezo1 mechanotransduction in articular chondrocytes as a pathogenic feed-forward mechanism in osteoarthritis. Proc Natl Acad Sci U S A. 2021 Mar 30;118(13).
• Nims RJ, Pferdehirt L, Ho NB, Savadipour A, Lorentz J, Sohi S, et al. A synthetic mechanogenetic gene circuit for autonomous drug delivery in engineered tissues. Sci Adv. 2021 Jan;7(5).
• Irwin RM, Puranam I, Hoffman BD, McNulty AL. DIFFERENTIAL RESPONSE OF INNER AND OUTER ZONE MENISCAL CELLS TO TENSILE LOAD UNDER NON-INFLAMMATORY AND INFLAMMATORY CONDITIONS. In: OSTEOARTHRITIS AND CARTILAGE. 2021. p. S3–4.
• Collins AT, Kulvaranon M, Spritzer CE, McNulty AL, DeFrate LE. The Influence of Obesity and Meniscal Coverage on In Vivo Tibial Cartilage Thickness and Strain. Orthop J Sports Med. 2020 Dec;8(12):2325967120964468.
• Hidalgo Perea S, Lyons LP, Nishimuta JF, Weinberg JB, McNulty AL. Evaluation of culture conditions for in vitro meniscus repair model systems using bone marrow-derived mesenchymal stem cells. Connect Tissue Res. 2020;61(3–4):322–37.
• Lyons LP, Hidalgo Perea S, Weinberg JB, Wittstein JR, McNulty AL. Meniscus-Derived Matrix Bioscaffolds: Effects of Concentration and Cross-Linking on Meniscus Cellular Responses and Tissue Repair. Int J Mol Sci. 2019 Dec 19;21(1).
• Ruprecht JC, Waanders TD, Rowland CR, Nishimuta JF, Glass KA, Stencel J, et al. Meniscus-Derived Matrix Scaffolds Promote the Integrative Repair of Meniscal Defects. Sci Rep. 2019 Jun 18;9(1):8719.
• DeFrate LE, Kim-Wang SY, Englander ZA, McNulty AL. Osteoarthritis year in review 2018: mechanics. Osteoarthritis Cartilage. 2019 Mar;27(3):392–400.
• Collins AT, Hatcher CC, Kim SY, Ziemian SN, Spritzer CE, Guilak F, et al. Selective Enzymatic Digestion of Proteoglycans and Collagens Alters Cartilage T1rho and T2 Relaxation Times. Ann Biomed Eng. 2019 Jan;47(1):190–201.
• Furman BD, Kent CL, Huebner JL, Kraus VB, McNulty AL, Guilak F, et al. CXCL10 is upregulated in synovium and cartilage following articular fracture. J Orthop Res. 2018 Apr;36(4):1220–7.
• Cao C, Ren Y, Mirando AJ, Barnett A, Rouse D, Mun SH, et al. Increased Ca2+signaling through altered CaV1.2 L-type Ca2+channel activity promotes bone formation and prevents estrogen deficiency-induced bone loss. In: JOURNAL OF BONE AND MINERAL RESEARCH. WILEY; 2017. p. S31–S31.
• Cao C, Ren Y, Barnett AS, Mirando AJ, Rouse D, Mun SH, et al. Increased Ca2+ signaling through CaV1.2 promotes bone formation and prevents estrogen deficiency-induced bone loss. JCI Insight. 2017 Nov 16;2(22).
• Liu B, Lad NK, Collins AT, Ganapathy PK, Utturkar GM, McNulty AL, et al. In Vivo Tibial Cartilage Strains in Regions of Cartilage-to-Cartilage Contact and Cartilage-to-Meniscus Contact in Response to Walking. Am J Sports Med. 2017 Oct;45(12):2817–23.
• Hatcher CC, Collins AT, Kim SY, Michel LC, Mostertz WC, Ziemian SN, et al. Relationship between T1rho magnetic resonance imaging, synovial fluid biomarkers, and the biochemical and biomechanical properties of cartilage. J Biomech. 2017 Apr 11;55:18–26.
• Liu B, Goode AP, Carter TE, Utturkar GM, Huebner JL, Taylor DC, et al. Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients. Connect Tissue Res. 2017;58(3–4):305–16.
• Rai MF, McNulty AL. Meniscus beyond mechanics: Using biology to advance our understanding of meniscus injury and treatment. Connect Tissue Res. 2017;58(3–4):221–4.
• Cucchiarini M, McNulty AL, Mauck RL, Setton LA, Guilak F, Madry H. Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus. Osteoarthritis Cartilage. 2016 Aug;24(8):1330–9.
• O’Conor CJ, Ramalingam S, Zelenski NA, Benefield HC, Rigo I, Little D, et al. Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis. Sci Rep. 2016 Jul 8;6:29053.
• Lee W, Leddy H, McNulty A, Guilak F, Liedtke W. Inflammatory Cytokine Il-1α Up-Regulates Piezo1 and Hyper-Sensitizes Chondrocytes to Compression. Biophysical Journal. 2016 Feb 16;110(3):349a-349a.
• McNulty AL, Guilak F. Mechanobiology of the meniscus. J Biomech. 2015 Jun 1;48(8):1469–78.
• Carter TE, Taylor KA, Spritzer CE, Utturkar GM, Taylor DC, Moorman CT, et al. In vivo cartilage strain increases following medial meniscal tear and correlates with synovial fluid matrix metalloproteinase activity. J Biomech. 2015 Jun 1;48(8):1461–8.
• McNulty AL, Leddy HA, Liedtke W, Guilak F. TRPV4 as a therapeutic target for joint diseases. Naunyn Schmiedebergs Arch Pharmacol. 2015 Apr;388(4):437–50.
• Lee W, Leddy HA, Chen Y, Lee SH, Zelenski NA, McNulty AL, et al. Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):E5114–22.
• Sanchez-Adams J, Leddy HA, McNulty AL, O’Conor CJ, Guilak F. The mechanobiology of articular cartilage: bearing the burden of osteoarthritis. Curr Rheumatol Rep. 2014 Oct;16(10):451.
• Leddy HA, McNulty AL, Lee SH, Rothfusz NE, Gloss B, Kirby ML, et al. Follistatin in chondrocytes: the link between TRPV4 channelopathies and skeletal malformations. FASEB J. 2014 Jun;28(6):2525–37.
• Leddy HA, McNulty AL, Guilak F, Liedtke W. Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias. Rare Dis. 2014;2(1):e962971.
• Chen Y, Williams SH, McNulty AL, Hong JH, Lee SH, Rothfusz NE, et al. Temporomandibular joint pain: a critical role for Trpv4 in the trigeminal ganglion. Pain. 2013 Aug;154(8):1295–304.
• McNulty AL, Rothfusz NE, Leddy HA, Guilak F. Synovial fluid concentrations and relative potency of interleukin-1 alpha and beta in cartilage and meniscus degradation. J Orthop Res. 2013 Jul;31(7):1039–45.
• Backus JD, Furman BD, Swimmer T, Kent CL, McNulty AL, Defrate LE, et al. Cartilage viability and catabolism in the intact porcine knee following transarticular impact loading with and without articular fracture. J Orthop Res. 2011 Apr;29(4):501–10.
• Riera KM, Rothfusz NE, Wilusz RE, Weinberg JB, Guilak F, McNulty AL. Interleukin-1, tumor necrosis factor-alpha, and transforming growth factor-beta 1 and integrative meniscal repair: influences on meniscal cell proliferation and migration. Arthritis Res Ther. 2011;13(6):R187.
• McNulty AL, Miller MR, O’Connor SK, Guilak F. The effects of adipokines on cartilage and meniscus catabolism. Connect Tissue Res. 2011;52(6):523–33.
• McNulty AL, Estes BT, Wilusz RE, Weinberg JB, Guilak F. Dynamic loading enhances integrative meniscal repair in the presence of interleukin-1. Osteoarthritis Cartilage. 2010 Jun;18(6):830–8.
• McNulty AL, Weinberg JB, Guilak F. Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus. Clin Orthop Relat Res. 2009 Jun;467(6):1557–67.
• Wilusz RE, Weinberg JB, Guilak F, McNulty AL. Inhibition of integrative repair of the meniscus following acute exposure to interleukin-1 in vitro. J Orthop Res. 2008 Apr;26(4):504–12.
• McNulty AL, Guilak F. Integrative repair of the meniscus: lessons from in vitro studies. Biorheology. 2008;45(3–4):487–500.
• McNulty AL, Moutos FT, Weinberg JB, Guilak F. Enhanced integrative repair of the porcine meniscus in vitro by inhibition of interleukin-1 or tumor necrosis factor alpha. Arthritis Rheum. 2007 Sep;56(9):3033–42.
• McNulty AL, Moutos FT, Wilusz RE, Weinberg JB, Guilak F. The effects of pro-inflammatory cytokines on functional repair of the meniscus. MCB Molecular and Cellular Biomechanics. 2006 Dec 1;3(4):197–8.
• McNulty AL, Stabler TV, Vail TP, McDaniel GE, Kraus VB. Dehydroascorbate transport in human chondrocytes is regulated by hypoxia and is a physiologically relevant source of ascorbic acid in the joint. Arthritis Rheum. 2005 Sep;52(9):2676–85.
• McNulty AL, Vail TP, Kraus VB. Chondrocyte transport and concentration of ascorbic acid is mediated by SVCT2. Biochim Biophys Acta. 2005 Jun 30;1712(2):212–21.
• Clark AG, Rohrbaugh AL, Otterness I, Kraus VB. The effects of ascorbic acid on cartilage metabolism in guinea pig articular cartilage explants. Matrix Biol. 2002 Mar;21(2):175–84.
• Michael NL, Louie LG, Rohrbaugh AL, Schultz KA, Dayhoff DE, Wang CE, et al. The role of CCR5 and CCR2 polymorphisms in HIV-1 transmission and disease progression. Nat Med. 1997 Oct;3(10):1160–2.
• DeFrate LE. IN VIVO STRAIN INCREASES FOLLOWING MEDIAL MENISCAL TEAR AND CORRELATES WITH SYNOVIAL FLUID MATRIX METALLOPROTEINASE ACTIVITY. Osteoarthritis and Cartilage.

In The News

• Artificial Scaffold Helps Cells Repair Torn Meniscus in Lab Tests (Jun 19, 2019 | Duke Health News)