Acceleration of bone regeneration by activating Wnt/β-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis

Abstract

By virtue of its excellent bioactivity and osteoconductivity, calcium phosphate cement (CPC) has been applied extensively in bone engineering. Doping a trace element into CPC can change physical characteristics and enhance osteogenesis. The trace element lithium has been demonstrated to stimulate the proliferation and differentiation of osteoblasts. We investigated the fracture-healing effect of osteoporotic defects with lithium-doped calcium phosphate cement (Li/CPC) and the underlying mechanism. Li/CPC bodies immersed in simulated body fluid converted gradually to hydroxyapatite. Li/CPC extracts stimulated the proliferation and differentiation of osteoblasts upon release of lithium ions (Li+) at 25.35 ± 0.12 to 50.74 ± 0.13 mg/l through activation of the Wnt/β-catenin pathway in vitro. We also examined the effect of locally administered Li+ on defects in rat tibia between CPC and Li/CPC in vivo. Micro-computed tomography and histological staining showed that Li/CPC had better osteogenesis by increasing bone mass and promoting repair in defects compared with CPC (P < 0.05). Li/CPC also showed better osteoconductivity and osseointegration. These findings suggest that local release of Li+ from Li/CPC may accelerate bone regeneration from injury through activation of the Wnt/β-catenin pathway in osteoporosis.

Yak (Bos grunniens) bones collagen‐derived peptides stimulate osteoblastic proliferation and differentiation via the activation of Wnt/β‐catenin signaling pathway

“…The phosphorylation of Akt at Ser473 residues may result in its activation, promoting GSK‐3 β phosphorylation and thereby inhibiting GSK‐3 β activity and activating the canonical Wnt/ β ‐catenin signaling. Our results are consistent with Li et al . who also demonstrated that lithium chloride / calcium phosphate cement increased the amount of phosphorylated GSK‐3 β significantly and decreased the amount of phosphorylated β ‐catenin, and subsequently stimulated the proliferation and differentiation of osteoblasts through activation of the Wnt/ β ‐catenin pathway in vitro .…”

Release of lithium from 3D printed polycaprolactone scaffolds regulates macrophage and osteoclast response

“…Conflicting data between in vitro and in vivo experiments has further complicated this issue [16,20,21,23,34]. In the literature, the effect of lithium-supplemented culture of BMSCs [34], pre-osteoblasts [20], and cementoblasts [16] has varied proliferation outcomes, with both increased and decreased responses reported.…”

“…Conflicting data between in vitro and in vivo experiments has further complicated this issue [16,20,21,23,34]. In the literature, the effect of lithium-supplemented culture of BMSCs [34], pre-osteoblasts [20], and cementoblasts [16] has varied proliferation outcomes, with both increased and decreased responses reported. While we demonstrated clear effects of lithium on macrophage response using our system, the mode of action of lithium in vivo is not well characterized across the literature, despite studies assessing lithium immunomodulation spanning the last 40 years [39][40][41].…”

Functionalization of Ceramic Coatings for Enhancing Integration in Osteoporotic Bone: A Systematic Review

“…The addition of platelet rich plasma (PRP) did not exert any trophic effects, probably because of difficulties in selecting the proper administration times, which should consider the different mechanism of actions [43]. Also, doping lithium (Li) onto CPC proved to induce early endochondral ossification and new bone formation in comparison to CPC alone, preserving the characteristics of bioactivity and biocompatibility of ceramic materials [44]. While Fang et al observed that the direct loading of simvastatin (SIM) on implants to substitute systemic administration alter the size of HA crystals, making them smaller and more irregular [45].…”