Coordination of Osteoblastogenesis and Osteoclastogenesis by the Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Matrix To Promote Bone Regeneration

Abstract

Extracellular matrix (ECM)-based therapies have been developed to improve bone repair because of their abundance of bioactive components. Besides the osteogenic promotion and the immune response, the potential effect of the ECM on the coordination between osteoblastogenesis and osteoclastogenesis in vivo should also deserve great attention because both osteoblasts and osteoclasts get involved in bone regeneration and are critical for the final repair outcome. Herein, based on our previous study on decellularization, antigen removal, and growth factor retention, porous poly (lactic-co-glycolic acid) (PLGA) scaffolds decorated with the bone marrow mesenchymal stem cell (BMSC)-derived ECM were prepared, and the functions of the ECM on BMSC osteogenic differentiation and osteoclastogenesis in vitro were preferentially investigated. Afterward, bone regeneration and osteoclast formation in vivo induced by ECM-decorated PLGA scaffolds were further studied. The in vitro tests revealed that ECM-decorated PLGA scaffolds obviously facilitated BMSC proliferation and osteogenic differentiation. However, when osteoclast precursors were cultured on the BMSC-derived ECM, the number and size of osteoclasts, expression of cathepsin K and matrix metalloproteinase 9, and tartrate-resistant acid phosphatase activity were notably decreased, accompanied by the reduction in the reactive oxygen species (ROS) level. Interestingly, the addition of exogenous hydrogen peroxide elevated the osteoclast amount on the ECM and up-regulated the resorption-related enzyme levels, implying that the repressive effect of the BMSC-derived ECM on osteoclasts may be related to the intracellular ROS. After implantation into calvarial defects, the ECM-decorated PLGA scaffolds significantly increased bone volume and bone mineral density compared with bare PLGA scaffolds and did not stimulate the overmuch formation of osteoclasts in vivo. This study evidenced that the BMSC-derived ECM may coordinate osteoblastogenesis and osteoclastogenesis and promote favorable bone formation without stimulating bone resorption.

Local exosomes and Hoxa11 status affect the healing fate during autogenous bone grafting at different sites

“…Due to the multidirectional differentiation potential and ability to release a variety of trophic factors and bioactive substances, clinical and animal studies have proven the efficacy of BMSCs at the healing edge of the bone transplantation area. 31,32 For the reparation and reconstruction of autografting, the migration, adherence, proliferation and differentiation of BMSCs is the first essential step, 33 which replaces lost cells in injured tissues and brings new regenerative power. In the defect area of bone tissue, BMSCs form clusters of high cellular density that outline the future bones.…”

Hepatocyte growth factor and insulin-like growth factor-1 were used to repair bone-cartilage defects in bone marrow mesenchymal stem cells in a rabbit model of postmenopausal

“…Treatment of women with PMOP remains challenging [2]. The process of bone repair starts with the differentiation of MSCs into osteoblasts and chondrocytes, followed by the synthesis of extracellular matrix to support continuous calcification and ossification [3][4][5][6]. However, postmenopausal osteoporosis patients have an imbalance in the aging and differentiation of bone marrow mesenchymal stem cells due to the loss of their own estrogen, making it difficult for their osteochondral defects to heal on their own [7][8][9][10].…”