Alleviation of Glucocorticoid-Induced Osteoporosis in Rats by Ethanolic Reynoutria multiflora (Thunb.) Moldenke Extract.

Secondary osteoporosis is frequently due to the use of high-dose glucocorticoids (GCs). The existing strategy for managing glucocorticoid-induced osteoporosis (GIOP) is considered insufficient and remains in a state of ongoing evolution. Therefore, it is crucial to develop more precise and effective agents for the treatment of GIOP. The constituents of Reynoutria multiflora (Thunb.) Moldenke, specifically Polygonum multiflorum (PM) Thunb, have previously shown promise in mitigating osteopenia. This study aimed to investigate the therapeutic effects of an ethanolic PM extract (PMR30) against GIOP in male rats. Prednisone (6 mg/kg/day, GC) was continuously administered to rats to induce GIOP, and they were subjected to treatment with or without ethanolic PMR30 for a duration of 120 days. Serum was collected for biochemical marker analysis. Bone histomorphometric, histological, and TUNEL analyses were performed on tibia samples. The protein expressions of LC3, Agt5, and Beclin 1 in the femur underwent examination through western blotting. Prolonged and excessive GC treatment significantly impeded bone formation, concomitant with reduced bone mass and body weight. It also suppressed OCN and OPG/RANKL in serum, and decreased Beclin 1 and LC3 in bone. Simultaneously, there was an elevation in bone resorption markers and apoptosis. Treatments with both high dose and low dose of PMR30 alleviated GIOP, stimulated bone formation, and upregulated OCN and OPG/RANKL, while suppressing TRACP-5b, CTX-I, and apoptosis. The impact of PMR30 possibly involves the enhancement of autophagy proteins (LC3, Agt5, and Beclin 1) and the inhibition of apoptosis within the bone. PMR30 holds promise as a prospective therapeutic agent for preventing and treating GIOP.

Pyrophosphorylated-Cholesterol-Modified Bone-Targeting Liposome Formulation Procedure.

Bone-targeting drug delivery systems have been rapidly developed to increase drug efficacy and safety for musculoskeletal diseases in the past decades. Bone-targeting drug delivery is mainly based on ligands that have hydroxyapatite affinity. We previously reported a pyrophosphorylated cholesterol ligand-based bone-targeting liposome formulation for the treatment of bone fracture delayed union. Different from traditional bone-targeting ligands: bisphosphonates tetracyclines and polyanion peptides. Pyrophosphorylated cholesterol has no intrinsic pharmacological effects and can be naturally degraded into metabolites (both pyrophosphate and cholesterol are substances that naturally exist in the body), leading to minimal safety concerns. Pyrophosphorylated cholesterol is not only biodegradable, but it also provides strong bone affinity, which could target different bone substructures/surfaces, further improving drug delivery efficiency in vivo. Here, we describe the synthesis protocol of pyrophosphorylated cholesterol and a reverse-evaporation-based formulation protocol of pyrophosphorylated-cholesterol-modified bone-targeting liposomes for hydrophilic drug encapsulation. We also provide instructions for the bone-targeting property evaluation of the pyrophosphorylated-cholesterol-modified liposome in vitro and in vivo. Our system has wide applications and has already been used to study drug treatment for fracture delayed union and nonunion. As a promising bone-targeting drug delivery system, our system may be extrapolated to clinical applications of other bone anabolic agents for different bone diseases.

Knee Osteoarthritis Therapy: Recent Advances in Intra-Articular Drug Delivery Systems.

Drug delivery for osteoarthritis (OA) treatment is a continuous challenge because of their poor bioavailability and rapid clearance in joints. Intra-articular (IA) drug delivery is a common strategy and its therapeutic effects depend mainly on the efficacy of the drug-delivery system used for OA therapy. Different types of IA drug-delivery systems, such as microspheres, nanoparticles, and hydrogels, have been rapidly developed over the past decade to improve their therapeutic effects. With the continuous advancement in OA mechanism research, new drugs targeting specific cell/signaling pathways in OA are rapidly evolving and effective drug delivery is critical for treating OA. In this review, recent advances in various IA drug-delivery systems for OA treatment, OA targeted strategies, and related signaling pathways in OA treatment are summarized and analyzed based on current publications.