The sensory nerve was recently identified as being involved in regulation of bone mass accrual. We previously discovered that prostaglandin E₂ (PGE2) secreted by osteoblasts could activate sensory nerve EP4 receptor to promote bone formation by inhibiting sympathetic activity. However, the fundamental units of bone formation are active osteoblasts, which originate from mesenchymal stromal/stem cells (MSCs). Here, we found that after sensory denervation, knockout of the EP4 receptor in sensory nerves, or knockout of COX-2 in osteoblasts, could significantly promote adipogenesis and inhibit osteogenesis in adult mice. Furthermore, injection of SW033291 (a small molecule that locally increases the PGE2 level) or propranolol (a beta blocker) significantly promoted osteogenesis and inhibited adipogenesis. This effect of SW033291, but not propranolol, was abolished in conditional EP4-KO mice under normal conditions or in the bone repair process. We conclude that the PGE2/EP4 sensory nerve axis could regulate MSC differentiation in bone marrow of adult mice.

Evidence links osteoporosis and cardiovascular disease but the cellular and molecular mechanisms are unclear. Here we identify skeleton-secreted platelet-derived growth factor–BB (PDGF-BB) as a key mediator of arterial stiffening in response to aging and metabolic stress. Aged mice and those fed high-fat diet (HFD), relative to young mice and those fed normal chow food diet, respectively, had higher serum PDGF-BB and developed bone loss and arterial stiffening. Bone/bone marrow preosteoclasts in aged mice and HFD mice secrete an excessive amount of PDGF-BB, contributing to the elevated PDGF-BB in blood circulation. Conditioned medium prepared from preosteoclasts stimulated proliferation and migration of the vascular smooth muscle cells. Conditional transgenic mice, in which PDGF-BB is overexpressed in preosteoclasts, had 3-fold higher serum PDGF-BB concentration and developed simultaneous bone loss and arterial stiffening spontaneously at a young age. Conversely, in conditional knockout mice, in which PDGF-BB is deleted selectively in preosteoclasts, HFD did not affect serum PDGF-BB concentration; as a result, HFD-induced bone loss and arterial stiffening were attenuated. These studies confirm that preosteoclasts are a main source of excessive PDGF-BB in blood circulation during aging and metabolic stress and establish the role of skeleton-derived PDGF-BB as an important mediator of vascular stiffening.

Background: Poly(vinyl alcohol) (PVA) hydrogels have been widely used in synthetic cartilage materials. However, limitations of PVA hydrogels such as poor biomechanics and limited cell ingrowth remain challenges in this field. Methods: This work aimed to design novel nano-hydroxyapatite (nano-HA)/poly(vinyl alcohol) (PVA) hydrogels coated with a poly(lactic-co-glycolic acid) (PLGA)/nano-HA/PVA scaffold to counter the limitations of PVA hydrogels. The core, comprising nano-HA/PVA hydrogel, had the primary role of bearing the mechanical load. The peripheral structure, composed of PLGA/nano-HA/PVA, was designed to favor interaction with surrounding cartilage. Results: The double-layer HA/PVA hydrogel coated with PLGA/HA/PVA scaffold was successfully prepared using a two-step molding method, and the mechanical properties and biocompatibility were characterized. The mechanical properties of the novel PLGA/HA/PVA scaffold modified HA/PVA hydrogel were similar to those of native cartilage and showed greater sensitivity to compressive stress than to tensile stress. Rabbit chondrocytes were seeded in the composites to assess the biocompatibility and practicability in vitro. The results showed that the peripheral component comprising 30 wt% PLGA/5 wt% HA/15 wt% PVA was most conducive to rabbit chondrocyte adhesion and proliferation. Conclusions: The study indicated that the double-layer HA/PVA hydrogel coated with PLGA/HA/PVA scaffold has the potential for cartilage repair.

Bone marrow edema (BME) of the femoral head is a prevalent condition that can cause hip pain and is observed in patients as a standalone finding or in conj