Biology subjects

Yeung, K. W. K.

Publications and source records attributed to Yeung, K. W. K..

2 recordsLinked to original sources

bioRxiv2021

SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters

Extrapulmonary complications of different organ systems have been increasingly recognized in patients with severe or chronic Coronavirus Disease 2019 (COVID-19). However, limited information on the skeletal complications of COVID-19 is known, even though inflammatory diseases of the respiratory tract have been known to perturb bone metabolism and cause pathological bone loss. In this study, we characterized the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bone metabolism in an established golden Syrian hamster model for COVID-19. SARS-CoV-2 causes significant multifocal loss of bone trabeculae in the long bones and lumbar vertebrae of all infected hamsters. The bone loss progressively worsens from the acute phase to the post-recovery phase. Mechanistically, the bone loss was associated with SARS-CoV-2-induced cytokine dysregulation which upregulates osteoclastic differentiation of monocyte-macrophage lineage. The pro-inflammatory cytokines further trigger a second wave of cytokine storm in the skeletal tissues to augment their pro-osteoclastogenesis effect. Our findings in this established hamster model suggest that pathological bone loss may be a neglected complication which warrants more extensive investigations during the long-term follow-up of COVID-19 patients. The benefits of potential prophylactic and therapeutic interventions against pathological bone loss should be further evaluated. O_FIG O_LINKSMALLFIG WIDTH=188 HEIGHT=200 SRC="FIGDIR/small/463665v1_ufig1.gif" ALT="Figure 1"> View larger version (81K): org.highwire.dtl.DTLVardef@ada9b8org.highwire.dtl.DTLVardef@1617fcaorg.highwire.dtl.DTLVardef@cdcd3org.highwire.dtl.DTLVardef@75a0ab_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical abstractSARS-CoV-2 infection causes pathological bone loss in golden Syrian hamsters through induction of cytokine storm and inflammation-induced osteoclastogenesis.

microbiology↗

bioRxiv2020

TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration

The use of magnesium ion (Mg2+)-modified biomaterials in bone regeneration is a promising and cost-effective therapeutic. Despite the widespread observation on the osteogenic effects of Mg2+, the diverse roles played by Mg2+ in the complex biological process of bone healing have not been systematically dissected. Here, we reveal a previously unknown biphasic mode of action of Mg2+ in bone repair. In the early inflammation phase, Mg2+ primarily targets the monocyte-macrophage lineage to promote their recruitment, activation, and polarization. We showed that an increase in extracellular Mg2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7) and a TRPM7-dependent influx of Mg2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines like IL-8, leading to the formation of a pro-osteogenic immune microenvironment. In the later active repair/remodeling phase of bone healing, however, continued exposure of Mg2+ and IL-8 leads to over activation of NF-{kappa}B signaling in macrophages, turning the immune microenvironment into pro-osteoclastogenesis. Moreover, the presence of Mg2+ at this stage also decelerates bone maturation through the suppression of hydroxyapatite precipitation. The negative effects of Mg2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg2+, as we found prolonged delivery of Mg2+ compromises overall bone formation. Taken together, this study establishes a paradigm shift in understanding the diverse and multifaceted roles of Mg2+ in bone healing.

cell biology↗