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November 28, 2024CellsOpen Access

CD38 Inhibitor 78c Attenuates Pro-Inflammatory Cytokine Expression and Osteoclastogenesis in Macrophages

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Authors

WLWilliam LoryNCNityananda ChowdhuryBWBridgette Wellslager

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Overview

Preclinical study demonstrates that CD38 inhibitor 78c suppresses inflammation and osteoclast formation in murine macrophages, highlighting potential therapeutic value for inflammatory bone loss.

Key Points

  • To evaluate the therapeutic effects of the CD38 inhibitor 78c on NAD+ replenishment, pro-inflammatory cytokine expression, and osteoclast differentiation in macrophages.
  • Treated murine bone marrow-derived macrophages (BMMs) with the CD38 inhibitor 78c or CD38 shRNA.
  • Challenged macrophages with oral pathogens (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans), advanced glycation end products (AGEs), or RANKL to assess inflammation and osteoclastogenesis.
  • Treatment with 78c dose-dependently reduced CD38, restored NAD+ depletion, and inhibited IL-1β, IL-6, and TNF-α expression induced by bacterial pathogens and AGEs.
  • 78c suppressed RANKL-mediated osteoclastogenesis, bone resorption, and podosome structural components while inhibiting NF-κB, PI3K, and MAPK signaling pathways.
  • CD38 knockdown via shRNA reduced only AGE-induced cytokines and enhanced RANKL-induced osteoclastogenesis, revealing that 78c likely exerts beneficial off-target effects.

Cite This Study

Lory et al. (2024) studied this question.

synapsesocial.com/papers/6a9cae9fa09733fe8776e468https://doi.org/10.3390/cells13231971
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Inhibition of CD38 by 78c Enhanced NAD+ and Alleviated Alveolar Bone Loss in Mice with Experimental Periodontitis2026
  2. 2Interleukin-38 promotes alveolar bone repair in periodontitis by suppressing the nuclear factor kappa B pathway2026
  3. 3Targeting CD38 for the prevention and treatment of Crohn’s disease-associated fibrosis2026
  4. 4Blockade of Cluster of Differentiation 38 Alleviates Sepsis-Induced Acute Lung Injury in Mice Through Inflammation Suppression via Regulating Toll-Like Receptor 4/Nuclear Factor kappa B p652024
  5. 5Macrophage CD38 overexpression drives primary platelet engraftment failure via paracrine suppression following allogeneic hematopoietic stem cell transplantation2025