Related Experiment Video
Updated: Jan 24, 2026

Modeling Primary Bone Tumors and Bone Metastasis with Solid Tumor Graft Implantation into Bone
Published on: September 9, 2020
Epigenetic drugs as new therapy for tumor necrosis factor-α-compromised bone healing
Tse-Hsiang Chen1, Franz E Weber2, Johann Malina-Altzinger3
1University of Zurich, Center of Dental Medicine, Oral Biotechnology & Bioengineering, Plattenstrasse11, 8032 Zürich, Switzerland; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Switzerland.
Abstract:
Impaired bone regeneration by excess inflammation leads to failure of bone healing. Current therapies display limited benefits making new treatments imperative. Our recent discoveries of the anti-inflammatory characteristics of bromodomain and extra terminal domain (BET) inhibitors, N-methylpyrrolidone (NMP) and N,N-Dimethylacetamide (DMA), implicate possible therapeutic use of epigenetic drugs in inflammation-impaired bone healing. Here, we investigated the effects of NMP and DMA on osteogenesis in vitro and ex vivo under the influence of TNFα, a key cytokine responsible for impaired fracture healing. NMP and DMA pre-treatment recovered TNFα-inhibited expression of essential osteoblastic genes, Alp, Runx2, and Osterix as well as mineralization in multipotent stem cells, but not in pre-osteoblasts and calvarial osteoblasts. The mechanism of action involves the recovery of TNFα-suppressed BMP-induced Smad signaling and the reduction of TNFα-triggered ERK pathway. In addition, ERK inhibitor treatment diminished the effect of TNFα on osteogenesis, which reinforces the role of ERK pathway in the adverse effect of TNFα. Furthermore, endochondral ossification was analyzed in an ex vivo bone culture model. TNFα largely abrogated BMP-promoted growth of mineralized bone while pre-treatment of NMP and DMA prevented the deleterious effect of TNFα. Taken together, these data shed light on developing low- affinity epigenetic drugs as new therapies for inflammation-compromised bone healing.
Related Concept Videos
Epigenetic Regulation
Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Factors Affecting Protein-Drug Binding: Drug-Related Factors
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In...
Drug Therapy
Antianxiety Medications
Factors Affecting α-Alkylation of Ketones: Choice of Base
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence,...
Factors Affecting Drug Distribution: Miscellaneous Factors
Age plays a significant role due to differences in body composition among different age groups. Infants, for instance, have a higher proportion of total body water and lower albumin levels, a protein that binds drugs in the bloodstream. This unique composition in infants enhances the...

