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Osteoarthritis

Clinical Trials

Phase 3: A Phase 3 Study Utilizing Patient-Reported and Radiograhic Outcomes and Evaluating the Safety and Efficacy of Lorecivivint (SM04690) for the Treatment of Moderately to Severely Symptomatic Knee Osteaoarthritis (STRIDES-X-ray)

Phase 2: A Study Evaluating the Safety, Tolerability and Efficacy of Two Injections of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

Phase 2: A Study Utilizing Imaging Techniques and Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

Phase 2: An Observational Study Evaluating the Safety, Tolerability, and Efficacy of Treatment of SM04690 or Placebo Previously Injected in the Target Knee Joint of Subjects With Moderately to Severely Symptomatic Osteoarthritis 

Phase 2: A Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis 

Phase 2: A Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects 

Phase 1: Phase 1, Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SM04690 in Moderate to Severe Knee Osteoarthritis (OA)

Press

Publications

International Workshop on Osteoarthritis Imaging (IWOAI) | June 26 - 29, 2019
Prince Edward Island, Canada

  • Optimizing Subject Selection in Knee Osteoarthritis Clinical Trials by Radiographic Joint Space Width: Post Hoc Clinical Response Analysis from a Phase 2b Trial of Wnt Pathway Inhibitor SM04690
    Abstract - Slides

European League Against Rheumatism (EULAR) | June 12 - 15, 2019
Madrid, Spain

  • Comparison of Knee Osteoarthritis Treatment Patterns by Rheumatologists vs. Other Providers in a U.S. Administrative Claims Database
    Abstract - Poster
  • Optimizing Subject Selection in Knee Osteoarthritis Clinical Trials by Radiographic Joint Space Width: Post Hoc Clinical Response Analysis from a Phase 2b Trial of Wnt Pathway Inhibitor Lorecivivint (SM04690)
    Abstract - Slides
  • Efficacy and Safety from a Phase 2b Trial of Lorecivivint (SM04690), a Novel Intra-articular Wnt Pathway Inhibitor for the Treatment of Osteoarthritis of the Knee
    Abstract - Poster
  • Comparison of Intra-articular Sham and Vehicle Injections from a Phase 2b Trial of Lorecivivint (SM04690), a Small-Molecule Wnt Pathway Inhibitor for Knee Osteoarthritis
    Abstract - Poster
  • Inhibition of CLK2 And DYRK1A by Lorecivivint (SM04690) as a Novel Molecular Regulator of Wnt Signaling, Chondrogenesis, and Inflammation, a Potential Disease-Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

Osteoarthritis and Cartilage | May 24, 2019

  • Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment

    Osteoarthritis and Cartilage. doi: 10.1016/j.joca.2019.05.006


    V. Deshmukh, A.L. O'Green, C. Bossard, T. Seo, L. Lamangan, M. Ibanez, A. Ghias, C. Lai, L. Do, S. Cho, J. Cahiwat, K. Chiu, M. Pedraza, S. Anderson, R. Harris, L. Dellamary, S. KC, C. Barroga, B. Melchior, B. Tam, S. Kennedy, J. Tambiah, J. Hood, Y. Yazici

    Article

International Society for Pharmaeconomics and Outcomes Research (ISPOR) | May 18 - 22, 2019
New Orleans, LA

  • An Analysis of Treatment Patterns in Knee Osteoarthritis in a U.S. Administrative Claims Database
    Abstract - Poster

Osteoarthritis Research Society International (OARSI) World Congress | May 02 - 05, 2019
Toronto, Canada

  • Efficacy and Safety from a Phase 2b Trial of Lorecivivint (SM04690), a Novel Intra-articular Wnt Pathway Inhibitor for the Treatment of Osteoarthritis of the Knee
    Abstract - Poster
  • Comparison of Intra-articular Sham and Vehicle Injection from a Phase 2b Trial of Lorecivivint (SM04690), a Small-Molecule Wnt Inhibitor, for Knee Osteoarthritis
    Abstract - Poster
  • Lorecivivint (SM04690), a Potential Disease-Modifying Treatment for Knee Osteoarthritis, Functions through Inhibition of CLK2 and DYRK1A, Novel Molecular Regulators of Wnt Signaling, Chondrogenesis, and Inflammation
    Abstract - Slides

Pan-American League of Associations for Rheumatology (PANLAR) | April 27 - 30, 2019
Quito, Ecuador

  • Efficacy and Safety from a Phase 2b Trial of Lorecivivint (SM04690), a Novel, Intra-articular Wnt Pathway Inhibitor for the Treatment of Osteoarthritis of the Knee
    Abstract - Poster

World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases | April 04 - 07, 2019
Paris, France

  • Modulation of the Wnt Pathway through Inhibition of CLK2 and DYRK1A by SM04690, a Novel Potential Disease-Modifying Treatment for Knee Osteoarthritis
    Abstract - Poster
  • Prospective Comparison of Intra-articular Sham vs. Placebo Injections: Data from a Randomized Controlled Phase 2b Trial of SM04690, a Wnt Pathway Inhibitor for Knee Osteoarthritis
    Abstract - Poster
  • Results from a Phase 2b Trial of SM04690, a Novel Intra-articular Wnt Pathway Inhibitor for the Treatment of Knee Osteoarthritis
    Abstract - Slides

Academy of Managed Care Pharmacy (AMCP) | March 25 - 28, 2019
San Diego, CA

  • An Analysis of the Burden of Illness and Treatment in Knee Osteoarthritis in a U.S. Administrative Claims Database
    Abstract - Poster

American Academy of Orthopaedic Surgeons (AAOS) | March 12 - 16, 2019
Las Vegas, NV

  • A 52-Week, Randomized, Double-Blind, Phase 2 Study of an Intra-articular Wnt Pathway Inhibitor (SM04690) for Osteoarthritis
    Abstract - Poster

Orthopaedic Research Society (ORS) | February 02 - 05, 2019
Austin, TX

  • SM04690, a Potential Disease-Modifying Treatment for Knee Osteoarthritis, Functions Through Inhibition of CLK2 and DYRK1A, Novel Molecular Regulators of Wnt Signaling, Chondrogenesis, and Inflammation
    Abstract - Poster

World Congress on Controversies, Debates & Consensus in Bone, Muscle & Joint Diseases (BMJD) | November 08 - 10, 2018
Bangkok, Thailand

  • Results from a 52-Week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Wnt Pathway Inhibitor (SM04690) for Knee Osteoarthritis Treatment
    Abstract - Poster
  • Joint Space Width Criteria Can Reduce Knee Osteoarthritis Trial Heterogeneity: Phase 2 Post-Hoc Data from Wnt Pathway Inhibitor SM04690
    Abstract - Poster
  • SM04690, A Wnt Pathway Inhibitor: Anti-Inflammatory and Cartilage Protective Effects in Preclinical OA Models
    Abstract - Poster
  • Radiographic Outcomes Were Concordant with Pain and Function Response: Post-Hoc Analysis from a Phase 2 Study of SM04690, a Wnt Pathway Inhibitor for Knee Osteoarthritis Treatment
    Abstract - Poster

American College of Rheumatology (ACR) | October 19 - 24, 2018
Chicago, IL

  • Efficacy and Safety from a Phase 2b Trial of SM04690, a Novel, Intra-Articular, Wnt Pathway Inhibitor for the Treatment of Osteoarthritis of the Knee
    Abstract - Poster
  • Treatment of Knee Osteoarthritis with SM04690 Improved WOMAC A1 “Pain on Walking” – Results from a 52-Week, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Wnt Pathway Inhibitor
    Abstract - Poster
  • Assessment of Health-Related Quality of Life in a 52-Week, Phase 2, Randomized, Controlled Trial of a Novel, Intra-Articular, Wnt Pathway Inhibitor (SM04690) for Treatment of Knee Osteoarthritis
    Abstract - Poster

Asia Pacific League of Associations for Rheumatology (APLAR) | September 06 - 09, 2018
Kaohsiung, Taiwan

  • Results from a 52-week, phase 2a study of an intra-articular, small molecule Wnt pathway inhibitor, SM04690, for knee osteoarthritis
    Abstract - Slides

International Workshop on Osteoarthritis Imaging (IWOAI) | July 05 - 07, 2018
Menton, France

  • Radiographic outcomes were associated with pain and function responses: post-hoc analysis from a phase 2 study of Wnt pathway inhibitor, SM04690, for knee osteoarthritis
    Abstract - Poster

European League Against Rheumatism (EULAR) | June 13 - 16, 2018
Amsterdam, Netherlands

  • Adjusting for the Intra-Articular Placebo Effect in Knee Osteoarthritis Therapies
    Abstract - Poster
  • Results from a 52-Week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Wnt Pathway Inhibitor (SM04690) for Knee Osteoarthritis Treatment
    Abstract - Poster
  • SM04690, a WNT Pathway Inhibitor: Anti-Inflammatory and Cartilage Protective Effects in Preclinical OA Models
    Abstract - Poster
  • Radiographic outcomes were associated with pain and function responses: post-hoc analysis from a phase 2 study of a Wnt pathway inhibitor, SM04690, for knee osteoarthritis treatment
    Abstract - Poster
  • Potential Nociceptive Pain Relief of Intra-Articular Saline Control in Clinical Trials of Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Trials
    Abstract - Poster
  • Treatment of Knee Osteoarthritis with SM04690 Improved WOMAC A1 “Pain on Walking” – Results from a 52 week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Wnt Pathway Inhibitor
    Abstract - Slides

The Orthobiologic Institute (TOBI) Annual Symposium | June 07 - 09, 2018
Las Vegas, NV

  • Results from a 52-Week, Phase 2a Study of an Intra-Articular, Wnt Pathway Inhibitor, SM04690, for Knee Osteoarthritis
    Abstract - Poster
  • SM04690, a Wnt Pathway Inhibitor: Anti-Inflammatory and Cartilage Protective Effects in Preclinical OA Models
    Abstract - Poster

Osteoarthritis Research Society International (OARSI) World Congress | April 26 - 29, 2018
Liverpool, United Kingdom

  • SM04690, a Wnt Pathway Inhibitor: Anti-Inflammatory and Cartilage Protective Effects in Preclinical Osteoarthritis Models
    Abstract - Poster
  • Radiographic Outcomes Were Concordant with Outcome Measures in Rheumatology Osteoarthritis Research Society International (OMERACT-OARSI) Strict Response: Post-Hoc Analysis from a Phase 2 Study of a Wnt Pathway Inhibitor, SM04690, for Knee Osteoarthritis Treatment
    Abstract - Poster
  • Joint Space Width Inclusion Criteria Can Reduce Knee Osteoarthritis Trial Heterogeneity: Post-Hoc Data from a Phase 2 Trial of Wnt Pathway Inhibitor, SM04690
    Abstract - Poster
  • Results from a 52-Week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular Wnt Pathway Inhibitor (SM04690) for the Treatment of Knee Osteoarthritis
    Abstract - Poster

World Congress on Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases | April 19 - 22, 2018
Krakow, Poland

  • Results from a 52 Week, Phase 2a Study of an Intra-Articular, Wnt Pathway Inhibitor, SM04690, for Knee Osteoarthritis
    Abstract - Slides
  • SM04690, a small molecule Wnt pathway inhibitor, appeared to have no deleterious effects on bone, joint, and tissue health in knee OA models
    Abstract - Poster
  • Joint Space Width Criteria Can Reduce Knee OA Trial Heterogeneity: Phase 2 Post-Hoc Data from Wnt Pathway Inhibitor, SM04690
    Abstract - Slides
  • SM04690, a Wnt Pathway Inhibitor: Anti-Inflammatory and Cartilage Protective Effects in Preclinical OA Models
    Abstract - Poster
  • SM04690 caused dose-dependent Wnt pathway modulation within a homeostatic range in a rat model of knee osteoarthritis
    Abstract - Poster

International Cartilage Repair Society (ICRS) | April 09 - 12, 2018
Macao, China

  • A 52 Week Randomized, Double-Blind Phase 2 Study of Intra-Articular, Wnt Pathway Inhibitor (SM04690) for Osteoarthritis
    Abstract - Slides
  • Joint Space Width Criteria Can Reduce Knee OA Trial Heterogeneity: P2 Post-Hoc Data from Wnt Pathway Inhibitor, SM04690
    Abstract - Slides
  • Radiographic Outcomes Were Concordant with Pain and Function Response: Post-Hoc Analysis from a Phase 2 Study of SM04690, a Wnt Pathway Inhibitor for Knee Osteoarthritis Treatment
    Abstract - Slides
  • SM04690, a Wnt Pathway Inhibitor: Anti-Inflammatory and Cartilage Protective Effects in Preclinical OA Models
    Abstract - Slides

Pan-American League of Associations for Rheumatology (PANLAR) | April 07 - 10, 2018
Buenos Aires, Argentina

  • Results from a 52-Week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular Wnt Pathway Inhibitor (SM04690) for the Treatment of Knee Osteoarthritis
    Abstract - Poster
  • SM04690, a Wnt Pathway Inhibitor: Anti-Inflammatory and Cartilage Protective Effects in Preclinical OA Models
    Abstract - Poster

Orthopaedic Research Society (ORS) | March 10 - 13, 2018
New Orleans, LA

  • Anti-Inflammatory Properties of SM04690, a Small Molecule Inhibitor of the Wnt Pathway as a Potential Treatment for Knee Osteoarthritis
    Abstract - Slides

American College of Rheumatology (ACR) | November 03 - 08, 2017
San Diego, CA

  • Results from a 52 Week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Wnt Pathway Inhibitor (SM04690) for the Treatment of Knee Osteoarthritis
    Abstract - Slides
  • Radiographic Outcomes Were Associated with Pain and Function Responses: Post-Hoc Analysis of Results from a Phase 2 Study of a Small Molecule Wnt Pathway Inhibitor, SM04690, for Knee Osteoarthritis Treatment
    Abstract - Poster
  • Reducing Heterogeneity in OA Clinical Trials: Data from a Phase 2 Study of SM04690, a Novel, Intra-Articular, Wnt Pathway
    Inhibitor in Knee Osteoarthritis
    Abstract - Poster

Orthopaedic Research Society (ORS) Southern California Regional Symposium | September 25, 2017
Los Angeles, CA

  • Cartilage Regeneration in a Rat Model of Knee OA by SM04690, a Potential Disease Modifying Wnt Pathway Inhibitor
    Abstract - Poster
  • Interim Results from a 52 week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Wnt Pathway Inhibitor (SM04690) for the Treatment of Knee Osteoarthritis
    Abstract - Poster

Osteoarthritis and Cartilage | September 15, 2017

  • A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee

    Osteoarthritis and Cartilage. doi: 10.1016/j.joca.2017.08.015


    V. Deshmukh, H. Hu, C. Barroga, C. Bossard, S. KC, L. Dellamary, J. Stewart, K. Chiu, M. Ibanez, M. Pedraza, T. Seo, L. Do, S. Cho, J. Cahiwat, B. Tam, J.R.S. Tambiah, J. Hood, N.E. Lane, Y. Yazici

    Article

Gordon Research Conference: Wnt Signaling | August 06 - 11, 2017
Stowe, VT

  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Poster - Slides

Osteoarthritis and Cartilage | July 13, 2017

  • A novel Wnt pathway inhibitor, SM04690, for the treatment of moderate to severe osteoarthritis of the knee: results of a 24-week, randomized, controlled, phase 1 study

    Osteoarthritis and Cartilage, 25(10), 1598-1606. doi:10.1016/j.joca.2017.07.006


    Y. Yazici, T.E. McAlindon, R. Fleischmann, A. Gibofsky, N.E. Lane, A.J. Kivitz, N. Skrepnik, E. Armas, C.J. Swearingen, A. DiFrancesco, J.R.S. Tambiah, J. Hood, M.C. Hochberg

    Article

International Cartilage Repair Society Heritage Summit | June 29 - Jul 01, 2017
Gothenburg, Sweden

  • Cartilage Regeneration in a Rat Model of Knee OA by SM04690, a Potential Disease Modifying Wnt Pathway Inhibitor
    Abstract - Poster

European League Against Rheumatism (EULAR) | June 14 - 17, 2017
Madrid, Spain

  • Anti-inflammatory Properties of SM04690, a Small Molecule Inhibitor of the Wnt Pathway as a Potential Treatment for Knee Osteoarthritis
    Abstract - Poster
  • Clinical Outcomes from a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Injectable, Wnt Pathway Inhibitor (SM04690) for the Treatment of Knee Osteoarthritis: Week 26 Interim Analysis
    Abstract - Poster
  • Radiographic Outcomes from a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Injectable, Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee: Week 26 Interim Analysis
    Abstract - Slides

International Society for Pharmacoeconomics and Outcomes (ISPOR) | May 20 - 24, 2017
Boston, MA

  • A Statistical Analysis Plan to Understand Osteoarthritis Patient Journey by Linking Medicare Claims Across Care Delivery Settings
    Abstract - Poster
  • Health Care Resource Use of Medicare Beneficiaries With Primary Osteoarthritis (OA) Of The Knee – A Claims Data Analysis
    Abstract - Poster

Musculoskeletal Regenerative Medicine and Biology: From Development to Regeneration | May 04 - 06, 2017
St. Louis, MO

  • Discovery of a Small Molecule Wnt Pathway Inhibitor (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Poster

Osteoarthritis Research Society International (OARSI) | April 27 - 30, 2017
Las Vegas, NV

  • Anti-inflammatory Properties of SM04690, a Small Molecule Inhibitor of the Wnt Pathway as a Potential Treatment for Knee Osteoarthritis
    Abstract - Poster

World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases | March 23 - 26, 2017
Florence, Italy

  • Discovery of a Small Molecule Wnt Pathway Inhibitor (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

Orthopaedic Research Society (ORS) | March 19 - 22, 2017
San Diego, CA

  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Poster

Musculoskeletal Development and Regeneration Conference (MDRC) | February 24 - 27, 2017
Cancun, Mexico

  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

American College of Rheumatology (ACR) | November 11 - 16, 2016
Washington D.C.

  • Radiographic Outcomes from a Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study of a Novel, Intra-Articular, Injectable, Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee
    Abstract - Poster
  • A Small Molecule, SM04690, Has Inhibitory Effects on the Wnt Pathway and Inflammation in Vitro, with Potential Implications for the Treatment of Osteoarthritis
    Abstract - Poster
  • Analysis of Pain and Function Components in Omeract-Oarsi Strict Responders from a Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study of a Novel, Intra-Articular, Injectable, Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee
    Abstract - Poster

International Cartilage Repair Society 2016 World Congress (ICRS) | September 24 - 27, 2016
Sorrento, Italy

  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

Royal Society of Medicine's 13th Medical Innovations Summit | September 17, 2016
London, United Kingdom

  • Samumed's Regenerative Medicine Platform
    Slides

European League Against Rheumatism (EULAR) | June 08 - 11, 2016
London, United Kingdom

  • Safety, Clinical and Imaging Outcomes of a Novel, Intra-Articular, Injectable, Wnt Inhbitor (SM04690) in the Treatment of Osteoarthritis of the Knee: Exploratory Analysis of Results from a 24 week, Randomized, Double-Blind, Placebo-Controlled Phase 1 Study
    Abstract - Poster
  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

Osteoarthritis Research Society International (OARSI) | March 31 - Apr 03, 2016
Amsterdam, Netherlands

  • OMERACT-OARSI ‘Strict Responders’ Analysis from Results of a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study of a Novel, Intra-Articular, Injectable Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee
    Abstract - Poster
  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

American College of Rheumatology (ACR) | November 06 - Oct 11, 2015
San Francisco, CA

  • Safety, Efficacy and Biomarker Outcomes of a Novel, Intra-Articular, Injectable, Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee: Interim, Exploratory Analysis of Results from a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study
    Abstract - Poster
  • Magnetic Resonance Imaging Outcomes Using an Intra-Articular Injection (SM04690) in the Treatment of Osteoarthritis of the Knee: Interim, Exploratory Analysis of Results from a Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study
    Abstract - Poster
  • Discovery of an Intra-Articular Injection Small Molecule Inhibitor of the Wnt Pathway (SM04690) As a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

Award Winning

Overview: Osteoarthritis

Knee Osteoarthritis

Arthritis is the most common cause of disability among adults, and osteoarthritis (OA) is the most common type of arthritis, accounting for much of this burden.1

  • The global prevalence of symptomatic knee OA has been estimated at 3.8% (4.8% for females and 2.8% for males).2
  • Current estimates indicate that there are 14 million US adults with symptomatic knee osteoarthritis.3 The overall number of US adults affected by OA in any joint has increased during recent decades and is estimated to affect 30 million US adults today, primarily due to an aging population and an ever-increasing prevalence of obesity.1
  • The combination of direct medical costs, pain and suffering, and loss of workplace productivity elevates OA to a major socioeconomic problem for health systems, the economy, and suffering patients.4

OA is characterized by the destruction of articular cartilage and structural changes in bone, which contribute to pain and loss of joint function.5 The Wnt signaling pathway plays a central role in the processes that direct the lineage fate of stem cells, that are resident in the joint, toward bone (osteoblasts) or cartilage (chondrocytes).6,7

  • In OA joints, elevated Wnt activity has been shown to cause these stem cells to become osteoblasts instead of chondrocytes and to lead to the production of proteases that degrade cartilage.8,9,10
  • Inhibition of Wnt signaling in OA joints may drive stem cells to become chondrocytes and block protease-mediated cartilage degradation, resulting in cartilage regeneration.8,11
  • Therapies that target the Wnt pathway may therefore have potential in treating OA.8

References

    1. Centers for Disease Control and Prevention. Osteoarthritis. Available at https://www.cdc.gov/arthritis/basics/osteoarthritis.htm.
    2. Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323-30.
    3. Deshpande BR, Katz JN, Solomon DH, et al. Number of persons with symptomatic knee osteoarthritis in the US: impact of race and ethnicity, age, sex, and obesity. Arthritis Care Res (Hoboken). 2016;68(12):1743-50.
    4. Wier LM, Levit K, Stranges E, et al. HCUP facts and figures: statistics on hospital based care in the United States, 2008. Rockville, MD: Agency for Healthcare Research and Quality, 2010. Available at http://www.hcup-us.ahrq.gov/reports/factsandfigures/2008/pdfs/FF_report_2008.pdf.
    5. Glyn-Jones S, Palmer AJR, Agricola R, et al. Osteoarthritis. Lancet. 2015;386(9991):376-87.
    6. Clevers H, Loh KM, Nusse R. Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science. 2014;346(6205):1248012.
    7. Blom AB, Brockbank SM, Van Lent PL, et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum. 2009;60(2):501-12.
    8. Monteagudo S, Lories RJ. Cushioning the cartilage: a canonical Wnt restricting matter. Nat Rev Rheumatol. 2017;13(11):670-81.
    9. Gelse K, Ekici AB, Cipa F, et al. Molecular differentiation between osteophytic and articular cartilage – clues for a transient and permanent chondrocyte phenotype. Osteoarthritis Cartilage. 2012;20(2):162-71.
    10. Corr M. Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis. Nat Clin Pract Rheumatol. 2008;4(10):550-6.
    11. Zimmerman ZF, Moon RT, Chien AJ. Targeting Wnt pathways in disease. Cold Spring Harb Perspect Biol. 2012;4(11):a008086.
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