scholarly journals Adipose-Derived Mesenchymal Stem Cells-Conditioned Medium Modulates the Expression of Inflammation Induced Bone Morphogenetic Protein-2, -5 and -6 as Well as Compared with Shockwave Therapy on Rat Knee Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1399
Author(s):  
Jai-Hong Cheng ◽  
Chieh-Cheng Hsu ◽  
Shan-Ling Hsu ◽  
Wen-Yi Chou ◽  
Yi-No Wu ◽  
...  

The dose-dependent effects of adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) were compared with those of shockwave (SW) therapy in the treatment of early osteoarthritis (OA). Anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was performed in rats divided into sham, OA, SW, CM1 (intra-articular injection of 100 μL ADSC-CM into knee OA), and CM2 (intra-articular injection of 200 μL ADSC-CM) groups. Cartilage grading, grading of synovium changes, and specific molecular analysis by immunohistochemistry staining were performed. The OARSI and synovitis scores of CM2 and SW group were significantly decreased compared with those of the OA group (p < 0.05). The inflammatory markers interleukin 1β, terminal deoxynucleotidyl transferase dUTP nick end labeling and matrix metalloproteinase 13 were significantly reduced in the CM2 group compared to those in the SW and CM1 groups (p < 0.001). Cartilage repair markers (type II collagen and SRY-box transcription factor 9, SOX9) expression were significantly higher in the CM2 group than in the other treatment groups (p < 0.001; p < 0.05). Furthermore, inflammation-induced growth factors such as bone morphogenetic protein 2 (BMP2), BMP5, and BMP6 were significantly reduced in the treatment groups, and the CM2 group showed the best results among the treatments (p < 0.05). In conclusion, ADSC-CM and SW ameliorated the expression of inflammatory cytokines and inflammation-induced BMPs to protect the articular cartilage of the OA joint.

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yoo-Kyung Sun ◽  
Jae-Kook Cha ◽  
Daniel Stefan Thoma ◽  
So-Ra Yoon ◽  
Jung-Seok Lee ◽  
...  

This study is designed to determine the effect of collagen membrane (CM) soaked with bone morphogenetic protein-2 (rhBMP-2) for the treatment of peri-implant dehiscence defects. Material and Methods. Three treatment groups were allocated at each defect in 5 dogs: (i) collagenated synthetic bone (OC) and CM soaked with rhBMP-2 (BMP group), (ii) OC and CM soaked with saline (nonBMP group), and (iii) no further treatment (control group). Titanium pins were used to stabilize the membranes in two dogs. Radiographic and histomorphometric analyses were performed 4 weeks later. Results. The median augmented volumes were 4.27 mm3, 6.24 mm3, and 2.75 mm3 in the BMP, nonBMP, and control groups, respectively; the corresponding median first bone-to-implant contact (fBIC) distances were 3.25 mm, 3.08 mm, and 2.56 mm (P>0.05). The placement of pins (with the BMP and nonBMP groups pooled) significantly improved bone regeneration: the augmented volumes were 17.60 mm3 with pins and 3.68 mm3 without pins (P=0.024), with corresponding fBIC distances of 2.25 mm and 3.31 mm, respectively (P<0.001). Conclusions. The addition of rhBMP-2 to CM failed to improve bone regeneration of peri-implant dehiscence defects compared to using an unsoaked CM after 4 weeks. However, the stabilization of CMs using pins positively influenced the outcomes.


2016 ◽  
Vol 25 (2) ◽  
pp. 154-164 ◽  
Author(s):  
John M. Zanella ◽  
Nahid Waleh ◽  
Juan Orduña ◽  
Jose Montenegro ◽  
Jaime Paulin ◽  
...  

OBJECTIVE It has been hypothesized that the recombinant human bone morphogenetic protein-2 (rhBMP-2) amplification of the host inflammatory response interacts with nerves in the spine and contributes to the occurrence of new, postoperative complaints of radiculitis. This in vivo rat study was conducted to assess the capacity for rhBMP-2/ACS (rhBMP-2 applied to absorbable collagen sponge [ACS]) to stimulate pain-associated behaviors in the rat chronic constriction injury (CCI) model. METHODS Rats were randomly assigned to one of 14 treatment groups. Half of the animals underwent a sham procedure in which the left sciatic nerve was exposed and manipulated but no ligature was placed (Sham cohort), while the remaining animals had chromic gut sutures tied around the sciatic nerve to induce CCI (CCI cohort). The following test articles were applied to the sciatic nerve in each cohort: saline alone, saline applied to ACS, 0.1 mg/ml rhBMP-2 applied to ACS, or 1.0 mg/ml rhBMP-2 applied to ACS. The ACS was either wrapped around the sciatic nerve or implanted adjacent to the nerve. Thermal withdrawal latency was assessed on Days 7, 14, 21, and 28 postoperatively. Isolated nerves from selected rats in each group were examined and assessed for histopathological changes on Days 3, 7, 14, and 28. RESULTS CCI produced a significant pain behavioral response for all treatment groups at all time points. In the Sham cohort, 0.1 mg/ml rhBMP-2/ACS wrapped around the nerve (WRP) decreased thermal withdrawal on Day 28, and 1.0 mg/ml rhBMP-2/ACS placed adjacent to the nerve (ADJ) decreased thermal withdrawal on Days 21 and 28. Conversely, in the CCI cohort, 0.1 mg/ml rhBMP-2/ACS ADJ increased thermal withdrawal latencies on Day 7; 1.0 mg/ml rhBMP-2/ACS ADJ increased thermal withdrawal latencies on Day 7; and 1.0 mg/ml rhBMP-2/ACS WRP increased thermal withdrawal on Days 7 and 14. Histologically, the effect of rhBMP-2 on nerve inflammation was unclear, as inflammatory cell infiltration was similar in the rhBMP-2/ACS and saline/ACS groups. rhBMP-2 was variably associated with bone formation within the epineurium at 14 days, and more prevalently at 28 days, with no clear relationship between dose or ACS positioning. CONCLUSIONS In this study, rhBMP-2/ACS did not appear to induce pain independent of grossly visible ectopic bone formation. At the earliest time points, rhBMP-2 appeared to have a neuroprotective effect as evidenced by decreased pain exhibited by the rhBMP-2–treated animals in the CCI cohort, but this effect diminished over time, and by Day 28, the pain behavioral responses in the rhBMP-2–treated group were comparable to those in the group in which saline was applied to the nerve. In the Sham cohort, there was a dose-independent induction of pain at later time points, presumably due to new bone formation mechanically irritating the nerve. Histological examination revealed nerve lesions that appeared to be caused by mechanical trauma associated with surgical manipulation of the nerve during placement of the ACS and/or CCI sutures.


2011 ◽  
Vol 14 (01) ◽  
pp. 1150001
Author(s):  
Yoshifumi Naka ◽  
Yusuke Hashimoto ◽  
Hiroaki Nakamura ◽  
Kunio Takaoka

Recombinant human bone morphogenetic protein-2 (rhBMP-2) (0, 0.1, 1, or 5 μg) was injected into the autogeneous semitendinosus tendon, and the tendon was transplanted to the region of the medial meniscus defect in a rabbit model to repair the defect. Cartilaginous transformation of the tendon by rhBMP-2 was expected under the less-vascularized intra-articular environment. At four and eight weeks after surgery, the left knee joints were harvested, and the morphological changes of the graft were examined by radiological, histological, and immunohistochemical methods. Cartilaginous tissue within the graft was detected by Safranin O staining and immunostaining of Type-II collagen. At four weeks, fibrocartilagenous tissue, together with small ossicles, was consistently noted in tendon autografts that were injected with 1 or 5 μg of rhBMP-2. At eight weeks, the cartilage located at the basal part of the graft adjacent to the joint capsule was partially replaced with ectopic bone in the 1-μg or 5-μg groups. The ossicles might have been formed by vascular invasion into the rhBMP-2-induced cartilage, but the cartilageous structure remained at the peripheral part of the graft and filled the meniscus defect. The experimental results indicate the potential use of rhBMP-2 in regenerating the cartilaginous meniscus if additional methods to suppress vascular invasion into the rhBMP-2–induced cartilage also inhibit ossification.


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