Targeting repairing cartilaginous and bony lesions by novel treatments

Abstract

Cartilage and bone are the important composites of joints that play a critical role for its functional and structural maintenance. Clinically, cartilaginous and bony lesions are very common that every year millions of individuals are affected globally. They could be caused by either osteoarthritis (OA) or trauma. The former was mainly characterized by the articular cartilage degenerations and abnormal remodeling of subchondral bone, which eventually results in cartilaginous and bony defect. The latter was more often caused by high-energy impacts among youth athletes. Therefore, this project was aimed at exploring novel treatments targeted at cartilaginous and bony lesions.

The present project was mainly consisted of three parts. In the first study, a canine surgically induced OA model was used, and zoledronate and high-dosed meloxicam were administrated in the early phase of disease. It was found that after these treatments OA progression was to some extent retarded instead of being totally prevented, but osteoarthritic lesions of cartilage were considerably alleviated. Microstructural analysis found that the use of both zoledronate and meloxicam could hardly inhibit bone loss, and in the very early phase of OA, significant increasement of PR ratio, i.e. plate-like trabeculae loss, was found in the whole progress of canine PTOA model. The obtained data indicated that zoledronate and high-dosed meloxicam could only alleviate, but not prevent the osteoarthritic lesions of cartilage and bone.

The second study focused on the treatment of cartilage lesion induced by trauma though inhibition of cellular senescence, because cellular senescence had been proved to be presented in both osteoarthritic and trauma-induced cartilaginous lesion and decrease chondrocytic capability of maintaining cartilaginous regeneration. A novel alginate (Alg)-based hydrogel encapsulated with metformin hydrochloride (MH) and strontium (Sr) was fabricated, and could significantly inhibit the senescent, apoptotic, oxidative and inflammatory genes’ expression of chondrocytes in vitro. The Alg/MH-Sr could also accelerate cartilage repairment and significantly inhibit chondrocytes’ senescence in vivo. These findings indicate that the Alg/MH-Sr is effective for cartilage lesion treatment, and provides a new clue in accelerating tissue repairment by inhibiting the senescence of cells and tissues.

In the third study, it was tried to repair bone lesion by a newly-synthesized scaffold with osteoimmunomodulatory capability, which had been found to be important in the regulation of bone metabolism during bone repairment. A strontium chondroitin sulfate (SrCS)-based chitosan (CH) scaffold was synthesized, and was found to down-regulate the expressions of osteoclastogenic markers of macrophages and the pro-inflammatory expression of MC3T3-E1 cells, but increase its expression of osteogenic genes. CH-SrCS could also enhance bone regeneration and increase bone volume in the bone lesional area. With all these constructive observations, it is believed that the CH-SrCS can be a promising candidate with improved osteoimmunomodulation for bone tissue engineering.