Increased Expression of Sox9 during Balance of BMSCs/Chondrocyte Bricks in Platelet-Rich Plasma Promotes Construction of a Stable 3-D Chondrogenesis Microenvironment for BMSCs

Abstract

Sox9 is an intrinsic transcription factor related to the determination and maintenance of chondrogenic lineage of bone marrow mesenchymal stem cells (BMSCs). In recent research, we have proved that fragmented chondrocyte aggregates (cell bricks) could promote chondrogenesis of BMSCs in vivo. However, it is still unknown whether the ratio of BMSCs/chondrocyte bricks has a significant influence on 3-D cartilage regeneration and related molecular mechanism. To address this issue, the current study subcutaneously injected three groups of cell complex with different rabbit BMSCs/chondrocyte bricks’ ratios (1 : 2, 1 : 1, and 2 : 1) into nude mice. Gross morphology observation, histological and immunohistochemical assays, biochemical analysis, gene expression analysis, and western blot were used to compare the influence of different BMSCs/chondrocyte bricks’ ratios on the properties of tissue-engineered cartilage and explore the related molecular mechanism. The constructs of 1 : 1 BMSCs/chondrocyte bricks, (B1CB1) group resulted in persistent chondrogenesis with appropriate morphology and adequate central nutritional perfusion without ossification. The related mechanism is that increased expression of Sox9 in the B1C1 group promoted chondrogenesis and inhibited the osteogenesis of BMSCs through upregulating Col-II as well as downregulating RUNX2 and downstream of Col-X and Col-I by upregulating Nkx3.2. This study demonstrated that BMSCs/chondrocyte bricks 1:1 should be a suitable ratio and the Sox9-Nkx3.2-RUNX2 pathway was a related mechanism which played an important role in the niche for stable chondrogenesis of BMSCs constructed by chondrocyte bricks and PRP.

Clinical Efficacy of Intra‐Articular Injection with P‐PRP Versus that of L‐PRP in Treating Knee Cartilage Lesion: A Randomized Controlled Trial

“…In addition, PRP also contains a variety of plasma proteins, which can promote the healing of fibrous connective tissue. Different from serum, plasma contains fibrinogen and some other coagulation factors, which can form fibrin scaffolds for cell adhesion, migration, and proliferation after activation 19,23,29,33,35,42,43 …”

“…Different from serum, plasma contains fibrinogen and some other coagulation factors, which can form fibrin scaffolds for cell adhesion, migration, and proliferation after activation. 19,23,29,33,35,42,43 Safety and Adverse Events Despite the benefit of PRP in treating cartilage lesions owing to the abundant growth factors, the clinical efficacy of PRP remains a controversial issue, mostly attributed to the different concentrations of leukocytes in PRP. In recent years, several subsequent studies have reported that despite its Fig.…”

“…[14][15][16] In the past few years, the application of PRP in the regeneration of cartilage lesions has proven to be simple, low-cost, and less invasive. [17][18][19][20][21][22] Initial studies have primarily demonstrated the feasibility and safety of PRP injection into the knee articular cavity for treating cartilage lesions, but several subsequent studies reported controversial therapeutic efficacy associated with the component of PRP, especially the different concentrations of leukocytes. 15,[23][24][25] Based on the concentration of leukocytes, PRP can be divided into two types: pure PRP (P-PRP) and leukocyte PRP (L-PRP).…”

Exosomes Derived from Runx2-Overexpressing BMSCs Enhance Cartilage Tissue Regeneration and Prevent Osteoarthritis of the Knee in a Rabbit Model

“…R-BMSCs-Exos avoid these shortcomings. 13 Stem Cells International BMSCs are isolated from bone marrow which is an ideal source of seed cells due to easy availability and high differentiation potential [27][28][29]. Tao et al found that synovial mesenchymal stem cells (SMSCs) can maintain their multidirectional differentiation potential after 10 th generation [30].…”

Berberine Encapsulated in Exosomes Derived from Platelet-Rich Plasma Promotes Chondrogenic Differentiation of the Bone Marrow Mesenchymal Stem Cells <i>via</i> the Wnt/β-Catenin Pathway

“…8) Several studies have demonstrated that the proliferative and synthesizing capacities of BMSCs are enhanced by PRP. [9][10][11] The administration of PRP could not only boost the formation of cartilage repair tissue but also could attain the quality of the level of native tissue. 12) Besides, PRP suppresses the catabolism of chondrocytes by the inflammatory cytokines, while simultaneously strengthening the synthesis of ECM and chondrogenesis.…”