Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice

Wang, Xiao; Li, Fengfeng; Xie, Liang; Crane, Janet L.; Zhen, Gehua; Mishina, Yuji; Deng, Ruoxian; Gao, Bo; Chen, Hao; Liu, Shen; Yang, Ping; Gao, Manman; Tu, Manli; Wang, Yiguo; Wan, Mei; Fan, Cunyi; Cao, Xu

doi:10.1038/s41467-018-02988-5

Cited by 164 publications

(173 citation statements)

References 69 publications

Supporting

Mentioning

159

Contrasting

Order By: Relevance

“…In addition, VEGF is essential for bone vascularization, fracture repair, and chondro-and osteogenic precursor function. Finally, the increased production of TGF-β found in our study correlates with recent findings where TGF-β levels are elevated in human heterotopic ossification and can trigger heterotopic ossification (25). Further investigation of whether local tissue-resident macrophages are affected by the ACVR1 R206H mutation, and whether communication with other immune cell lineages occurs, remain important challenges to overcome.…”

Section: I N I C a L M E D I C I N Esupporting

confidence: 87%

“…We found a trend toward elevated levels of TGF-β1 in stimulated FOP macrophages, but it was not statistically significant, likely due to biological variability. These results suggest that M2 macrophages may contribute to the fibrosis (70, 71) seen in developing heterotopic ossification lesions (25). Phagocytic abilities of FOP macrophages showed no major differences from control macrophages (Supplemental Figure 6).…”

Section: I N I C a L M E D I C I N Ementioning

confidence: 70%

“…Mouse models of heterotopic ossification also show that macrophages and TGF-β are important regulators of heterotopic ossification (24,25). Trauma-induced heterotopic ossification from hind limb Achilles' tenotomy and dorsal burns in mice cause increased levels of TNF-α and IL-1β within 48 hours after injury, with persistent MCP1 and VEGF elevations detectable in saliva 1 week after injury (26).…”

Section: Resultsmentioning

confidence: 99%

“…Our supernatant analysis showed evidence of functional differences between FOP and control macrophages. Macrophages can produce TGF-β, a secreted protein implicated in fibrosis and heterotopic ossification (25,70). TGFB expression was significantly increased in FOP antiinflammatory M2 macrophages upon LPS stimulation ( Figure 8A).…”

Section: I N I C a L M E D I C I N Ementioning

confidence: 99%

“…MIP1-β, eotaxin, and GROα are upregulated during the acute phase of fracture healing (90). PDGFBB + cells and PDGFBB in serum are increased during heterotopic ossification progression (25). PDGFs, which can be produce by macrophages (91), are chemoattractant for osteoprogenitors (92) and may recruit mesenchymal cells and osteoprogenitors to form heterotopic ossification.…”

Section: I N I C a L M E D I C I N Ementioning

confidence: 99%

See 4 more Smart Citations

NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification

Barruet¹,

Morales²,

Cain³

et al. 2018

JCI Insight

View full text Add to dashboard Cite

Statistics. All studies were performed with biological replicates as described in Supplemental Tables 1-11. The data were analyzed with GraphPad Prism v.7 software using 2-tailed Student's t test and 2-way ANOVA Sidak or Tukey's multiple comparison tests. The Sidak test was used when comparing means between WT and FOP, and the Tukey test was used when means of both WT and FOP were compared together with other groups. The software R was used for heatmaps and PCA. P < 0.05 were considered statistically significant. Study approvals. All of the human study and sample collection procedures were reviewed and approved by the UCSF Committee on Human Research. All subjects provided informed consent prior to their participation in the study.

show abstract

Section: I N I C a L M E D I C I N Esupporting

confidence: 87%

Section: I N I C a L M E D I C I N Ementioning

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: I N I C a L M E D I C I N Ementioning

confidence: 99%

Section: I N I C a L M E D I C I N Ementioning

confidence: 99%

See 3 more Smart Citations

NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification

Barruet¹,

Morales²,

Cain³

et al. 2018

JCI Insight

View full text Add to dashboard Cite

show abstract

Enzyme‐Photodynamic Adaptive Bionic Periosteum for Bone Revitalization

Chen,

Jin,

et al. 2024

Adv Funct Materials

View full text Add to dashboard Cite

The lack of periosteum in bone allografts is considered a major cause of bone graft failure; however, the currently used artificial periosteum has failed to proactively adapt to its chronological role in the repair process. This study designed an adaptive periosteal system with dual‐response mechanisms to enable interactive angiogenic/osteogenic stimulation customized for inflammatory and anabolic stages of bone healing. Utilizing the enzymatic reactions and photodynamic properties of gold nanorod‐porous silicon, angiogenic peptides (QK) are released in response to matrix metalloproteinase 2 (MMP‐2), whereas bone‐forming peptides (BFP) are triggered by timed near‐infrared (NIR) irradiation, providing a portfolio of growth factors that match the dynamics of bone healing. The incorporation of such nanocarriers into a poly(N‐isopropyl acrylamide)/methacrylic acid gel (PNIPAM/GelMA) successfully formed a bionic periosteum that actively adapted to the function of the periosteum in different scenarios, resulting in more than doubled its ability to promote angiogenesis, stem cell migration, and osteogenesis compared to the controls. Furthermore, over 80% of the defects are covered with a new scab after the timed near‐infrared irradiation of large bone defects implanted with the system. The bionic periosteum actively mimicked the role of the periosteum in bone healing and offered a novel selection strategy for adaptability.

show abstract

Human Tendon‐on‐a‐Chip for Modeling the Myofibroblast Microenvironment in Peritendinous Fibrosis

Ajalik,

Linares,

Alenchery

et al. 2024

Adv Healthcare Materials

View full text Add to dashboard Cite

Understanding the myofibroblast microenvironment is critical to developing therapies for fibrotic diseases. Here the development of a novel human tendon‐on‐a‐chip (hToC) is reported to model this crosstalk in peritendinous adhesions, which currently lacks biological therapies. The hToC facilitates cellular and paracrine interactions between a vascular component, which contains endothelial cells and monocytes, and a tissue hydrogel component that houses tendon cells and macrophages. It is found that the hToC replicates some aspects of in vivo inflammatory and fibrotic phenotypes in preclinical and clinical samples, including activated mTOR signaling, vascular inflammation, tissue contraction induced by myofibroblast activation, inflammatory cytokines secretion, and transendothelial migration of monocytes to the tissue hydrogel. Transcriptional analysis demonstrates significant overlap in enriched pathways in the hToC with human tenolysis samples, including the activation of mTOR signaling. Rapamycin suppresses the vascular inflammation and fibrotic phenotype in the hToC, which provides proof‐of‐concept of its utility as an in vitro tool for investigating multicellular crosstalk in fibrosis and testing therapeutics to mitigate it.

show abstract

Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice

Cited by 164 publications

References 69 publications

NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification

NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification

Enzyme‐Photodynamic Adaptive Bionic Periosteum for Bone Revitalization

Human Tendon‐on‐a‐Chip for Modeling the Myofibroblast Microenvironment in Peritendinous Fibrosis

Contact Info

Product

Resources

About