Abstract Number: 891 • 2019 ACR/ARP Annual Meeting
Lorecivivint (SM04690), a Potential Disease-Modifying Osteoarthritis Drug, Inhibits CLK2 and DYRK1A, Novel Molecular Regulators of Wnt Signaling, Chondrogenesis, and Inflammation
Background/Purpose: In the synovial joint, Wnt pathway upregulation contributes to osteoarthritis (OA) by increasing osteocyte differentiation, cartilage thinning, and inflammation. Lorecivivint (LOR; SM04690), a novel…Abstract Number: 1326 • 2019 ACR/ARP Annual Meeting
Safety Profile to Date of the Novel, Intra-articular Agent Lorecivivint (LOR; SM04690), a CLK/DYRK1A Inhibitor That Modulates the Wnt Pathway, in Subjects with Knee Osteoarthritis
Background/Purpose: Recent concerns over osteoarthritis (OA) pharmacotherapy safety have led to revision of treatment guidelines and highlight the need for therapies with good safety profiles.…Abstract Number: 1327 • 2019 ACR/ARP Annual Meeting
The Novel, Intra-articular CLK/DYRK1A Inhibitor Lorecivivint (LOR; SM04690), Which Modulates the Wnt Pathway, Improved Responder Outcomes in Subjects with Knee Osteoarthritis: A Post Hoc Analysis from a Phase 2b Trial
Background/Purpose: Lorecivivint (LOR, SM04690) is a small-molecule, intra-articular (IA) CLK/DYRK1A inhibitor which modulates the Wnt pathway and has demonstrated beneficial effects on patient-reported outcomes (PROs)…Abstract Number: 1435 • 2019 ACR/ARP Annual Meeting
Acute Effects of IL-6 Blockade, TNFα Inhibitor or Glucocorticoids on Bone Turnover Markers and Wnt Inhibitors in Early Rheumatoid Arthritis
Background/Purpose: Wnt signaling is an important regulator of bone remodeling and it is involved in the pathogenesis of focal and systemic bone loss in Rheumatoid…Abstract Number: 1770 • 2019 ACR/ARP Annual Meeting
Experimental Rheumatoid Joint Ameliorated by CRISPR Interference Targeting Long Non-coding RNA H19 Through Wnt Signaling Inactivation
Background/Purpose: Long non-coding RNAs (lncRNAs) participate in the rheumatoid arthritis (RA) pathogenesis. The aim of this study was to examine the lncRNA H19 and HOTAIR…Abstract Number: L03 • 2018 ACR/ARHP Annual Meeting
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
Background/Purpose: A previous Phase 2a study of SM04690, a small molecule, intra-articular (IA), Wnt pathway inhibitor, demonstrated positive effects on knee OA pain, physical function,…Abstract Number: 1047 • 2018 ACR/ARHP Annual Meeting
Signaling at Adenosine A2A Receptor (A2aR) in Osteoblasts; Crosstalk with Wnt/ β-Catenin Signaling Pathway
Background/Purpose: The Wnt/β-catenin signaling pathway plays a key role in regulating bone formation and maintaining bone hemostasis. Wnt activates a pathway that leads to stabilization…Abstract Number: 1904 • 2018 ACR/ARHP Annual Meeting
Orphan Nuclear Receptor Rorα Is a Key Regulator of Tgfβ- and WNT-Signaling in Fibrotic Diseases
Background/Purpose: The Retinoic-acid related Orphan Receptor-alpha (RORα) is a member of the nuclear receptor superfamily and a ligand-dependent transcription factor implicated in a wide range…Abstract Number: 1985 • 2018 ACR/ARHP Annual Meeting
IL-1β Inhibits the Expression of Dickkopf-1, an Antagonist of the Wnt-β-Catenin Signaling Pathway: A Possible Role of Inflammasome in Dysregulation of Endochondral Ossification
Background/Purpose: Aberrant endochondral bone formation in the physis is a unique bone lesion in neonatal-onset multisystem inflammatory disease (NOMID), also called chronic infantile neurologic cutaneous…Abstract Number: 1716 • 2017 ACR/ARHP Annual Meeting
TGFβ-Dependent Upregulation of XIAP Fosters Fibroblast Activation and Tissue Fibrosis By Promoting Canonical Wnt Signaling
Background/Purpose: Aberrant activation of profibrotic pathways is a key feature of systemic sclerosis (SSc). Extensive evidence characterizes TGFβ- and canonical WNT-signaling as key drivers of…Abstract Number: 1924 • 2017 ACR/ARHP Annual Meeting
The Nuclear Receptor ROR-Alpha As a Key Checkpoint of Tissue Repair
Background/Purpose: The Retinoic-acid related Orphan Receptor-alpha (RORα) is a member of the nuclear receptor superfamily and a ligand-dependent transcription factor implicated in a wide range…Abstract Number: 2929 • 2017 ACR/ARHP Annual Meeting
WNT5A Promotes Tissue Fibrosis By Wnt/PCP-Dependent Activation of Latent TGF-β
Background/Purpose: Canonical Wnt/β-catenin signaling has emerged as a core pathway of fibrosis. They role of non-canonical Wnt signaling, however, has not been systematically studied. In…Abstract Number: 903 • 2017 ACR/ARHP Annual Meeting
Increased Expression of CCN4/WISP1 in Osteoarthritic Articular Cartilage Is Epigenetically Regulated and Disrupts Cartilage Homeostasis
Background/Purpose: Previously, we described increased expression of Wnt-1-induced signaling protein 1 (Wisp1) in murine synovium and cartilage after induction of experimental osteoarthritis (OA) models. WISP1…Abstract Number: 935 • 2017 ACR/ARHP Annual Meeting
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
Background/Purpose: Knee osteoarthritis (OA) is characterized by pain, disability and joint deformity due to articular cartilage degradation and bone remodeling. Wnt signaling is involved in…Abstract Number: 1201 • 2017 ACR/ARHP Annual Meeting
Reducing Heterogeneity in OA Clinical Trials: Data from a Phase 2 Study of SM04690, a Novel, Intra-Articular, Wnt Pathway Inhibitor in Knee Osteoarthritis
Background/Purpose: Kellgren-Lawrence [KL] radiographic grading is used to classify knee osteoarthritis (OA), but may not accurately reflect disease progression. Classifying subjects by baseline medial joint…
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