miR-188-3p targets skeletal endothelium coupling of angiogenesis and osteogenesis during ageing

Abstract

A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin β3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.

MicroRNA‐7 deficiency ameliorates d‐galactose‐induced aging in mice by regulating senescence of Kupffer cells

“…| 11 of 18 WANG et al (Srinivasan et al, 2022), miR-188-3p (He et al, 2022), and miR-21 (Xiong et al, 2021) have been implicated in the regulation of the aging process. Collectively, these studies highlight the critical regulatory role of non-coding RNA molecules, represented by miR-7, in the aging process.…”

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing

“…Fractured bones were dissected at various time intervals and fixed for 24 hours with 4% paraformaldehyde, following scanned and analyzed with high-resolution micro-computed tomography (μCT) (Skyscan 1172, Bruker MicroCT, Kontich, Belgium) as previous reported 54 , 55 . The callus index (CI) of fractured bone was evaluated by calculating the ratio of the maximal diameter of the callus to the diameter of the adjacent diaphysis.…”

“…Immunofluorescence staining was conducted as previously described 54 , 55 . Briefly, femora were treated for antigen retrieval by digestion with 0.05% trypsin at 37 °C for 15 minutes, and stained with primary antibodies, including anti-Ctsk (ab19027, 1:200, Abcam), anti-GFP (ab6673, 1:200, Abcam), and anti-Ocn (M137, 1:500, Takara) overnight at 4 °C.…”

Role of miRNA-regulated type H vessel formation in osteoporosis

“…They suggested that miRNA-188-3p directly targets integrin b3 in endothelial cells, inhibiting type H vessel formation and contributing to age-related type H vessel decline. By contrast, knocking out miRNA-188 can alleviate the type H vessel decline in aged mice (46).…”

“…For endothelial cells, adhesion to ECM via cell-surface integrins is necessary for endothelial cell proliferation and angiogenesis (45). Previous studies showed that integrins, such as integrin b1 and integrin b3, also exist in type H endothelial cells and play a crucial role in angiogenesis (46). He and colleagues found specific overexpression of miRNA-188-3p in the senescent endothelial cells of type H vessels, which inhibits the type H vessel formation, especially in aged mice.…”