Osteoclasts protect bone blood vessels against senescence through the angiogenin/plexin-B2 axis

Abstract

Synthetic glucocorticoids (GCs), one of the most effective treatments for chronic inflammatory and autoimmune conditions in children, have adverse effects on the growing skeleton. GCs inhibit angiogenesis in growing bone, but the underlying mechanisms remain unclear. Here, we show that GC treatment in young mice induces vascular endothelial cell senescence in metaphysis of long bone, and that inhibition of endothelial cell senescence improves GC-impaired bone angiogenesis with coupled osteogenesis. We identify angiogenin (ANG), a ribonuclease with pro-angiogenic activity, secreted by osteoclasts as a key factor for protecting the neighboring vascular cells against senescence. ANG maintains the proliferative activity of endothelial cells through plexin-B2 (PLXNB2)-mediated transcription of ribosomal RNA (rRNA). GC treatment inhibits ANG production by suppressing osteoclast formation in metaphysis, resulting in impaired endothelial cell rRNA transcription and subsequent cellular senescence. These findings reveal the role of metaphyseal blood vessel senescence in mediating the action of GCs on growing skeleton and establish the ANG/PLXNB2 axis as a molecular basis for the osteoclast-vascular interplay in skeletal angiogenesis.

Myeloid‐derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation

“…Meanwhile, the abundance of osteoclast progenitors (CD14 + ) was not altered as detected by flow cytometry (Fig EV2D and E). Knowing that bone vascularization is critical for bone health (Yang et al , 2020; Liu et al , 2021), bone tissue sections of CKO and WT mice were co‐stained with CD31, a specific vascular endothelial surface marker, and endomucin (Emcn), a specialized capillary subtype coupling angiogenesis and osteogenesis. Results showed that the abundance of CD31 hi Emcn hi vessels was similar between CKO and WT mice at 2 weeks, and profoundly reduced in 3‐month‐old CKO mice compared with WT mice (Fig EV2F and G).…”

Evaluation of Glucocorticoid Therapy in Asthma Children with Small Airway Obstruction Based on CT Features of Deep Learning

“…Childhood asthma is a “bad child condition” that predicts pulmonary function and airflow limitation in early adulthood. First, the related decline in pulmonary function may begin in infancy or fetus and continue to childhood and adulthood [ 12 ]. According to newspaper reports, asthma is associated with persistent low pulmonary function.…”

Skeleton-secreted PDGF-BB mediates arterial stiffening

“…All sections were observed using an Olympus BX51 microscope. Quantitative histomorphometry analyses were performed as described previously (85) in a blinded fashion using OsteoMeasure Software (OsteoMetrics, Inc.). The sample area selected for calculation was a 1 mm 2 area within the metaphyseal trabecular bone.…”