Expression of Bone Morphogenetic Protein-2 in the Chondrogenic and Ossifying Sites of Calcific Tendinopathy and Traumatic Tendon Injury Rat Models

<p>Abstract</p> <p>Background</p> <p>Ectopic chondrogenesis and ossification were observed in a degenerative collagenase-induced calcific tendinopathy model and to a lesser extent, in a patellar tendon traumatic injury model. We hypothesized that expression of bone morphogenetic protein-2 (BMP-2) contributed to ectopic chondrogenesis and ossification. This study aimed to study the spatial and temporal expression of BMP-2 in our animal models.</p> <p>Methods</p> <p>Seventy-two rats were used, with 36 rats each subjected to central one-third patellar tendon window injury (C1/3 group) and collagenase-induced tendon injury (CI group), respectively. The contralateral limb served as controls. At week 2, 4 and 12, 12 rats in each group were sacrificed for immunohistochemistry and RT-PCR of BMP-2.</p> <p>Results</p> <p>For CI group, weak signal was observed at the tendon matrix at week 2. At week 4, matrix around chondrocyte-like cells was also stained in some samples. In one sample, calcification was observed and the BMP-2 signal was observed both in the calcific matrix and the embedded chondrocyte-like cells. At week 12, the staining was observed mainly in the calcific matrix. Similar result was observed in C1/3 group though the immunopositive staining of BMP-2 was generally weaker. There was significant increase in BMP-2 mRNA compared to that in the contralateral side at week 2 and the level became insignificantly different at week 12 in CI group. No significant increase in BMP-2 mRNA was observed in C1/3 group at all time points.</p> <p>Conclusion</p> <p>Ectopic expression of BMP-2 might induce tissue transformation into ectopic bone/cartilage and promoted structural degeneration in calcific tendinopathy.</p

The non-reconstructive treatment of complete ACL tear with biological enhancement in clinical and preclinical studies: A systematic review

Introduction: There is still controversy regarding the bio-enhanced non-reconstructive ACL treatment. Materials and methods: A search for articles in databases was performed in February 2017. The objective and subjective evaluations of clinical studies and biomechanical and histological data of preclinical studies were extracted. Results: Eighteen articles were included for analysis. In clinical studies, although subjective scores were significantly improved, the rate of re-operation rate was high. In preclinical studies, bio-enhancing techniques demonstrated promotion of the healing of ACL. Conclusions: The efficacy of biological enhancement cannot be validated in clinical studies. Preclinical studies showed improved biomechanical and healing potential

Muscle-Secreted Factors Improve Anterior Cruciate Ligament Graft Healing: An In Vitro and In Vivo Analysis

One of the ligaments most often damaged during sports - the anterior cruciate ligament (ACL) - has poor healing capacity. On damage, reconstructive surgery is performed to restore the mechanical stability of the knee and to reduce the inflammatory milieu otherwise present in the joint. A return to normal activities, however, takes between 9 and 12 months. Thus, strategies capable of improving ACL graft healing are needed. Embryonic development of tendon and ligament (T/L) is regulated by a crosstalk between different cell types. We hypothesized that terminally differentiated skeletal-derived cells such as osteoblasts, chondrocytes, and myoblasts modulate T/L healing. Using an indirect coculture system, we discovered that myoblast-secreted signals - but not osteoblasts, chondrocytes, or stromal-secreted signals - are capable of upregulating classical T/L markers such as scleraxis and tenomodulin on human hamstring tendon-derived cells (hTC), which contribute to ACL graft healing. Transcriptome analysis showed that coculturing hTC with myoblasts led to an upregulation of extracellular matrix (ECM) genes and resulted in enhanced ECM deposition. In vivo, using a rat model of ACL reconstruction showed that conditioned media derived from human muscle tissue accelerated femoral tunnel closure, a key step for autograft integration. Collectively, these results indicate that muscle-secreted signals can be used to improve ACL graft healing in a clinical setting where muscle remnants are often discarded

Intra-articular injection of an antioxidant formulation did not improve structural degeneration in a rat model of post-traumatic osteoarthritis

Background/objective: Oxidative stress plays an important role in osteoarthritis (OA), causing inflammation and matrix degradation in joints. Previous studies have shown that antioxidants such as quercetin and vitamin C are potential candidates for treating OA. We aimed to determine whether a formulation of quercetin and vitamin C, together with an iron chelator, could retard OA progression in a post-traumatic OA rat model. Methods: Twelve rats received anterior cruciate ligament transection for OA induction. At 20 weeks postoperation, weekly intra-articular injection of 50 μL of either saline or a formulation of quercetin dehydrate, sodium-L-ascorbate, and deferoxamine mesylate was given consecutively for 4 weeks (n=5). Gait analysis was performed at pretreatment, and at 1 week and 5 weeks post-treatment. Microcomputed tomography scanning and histological scoring were performed at 5 weeks post-treatment. Results: Gait analysis showed that intra-articular injections of antioxidant formulation did not improve pain-associated Limb Idleness Index over time (p=0.449, Friedman test). However, at 5 weeks post-treatment, the treatment group exhibited a significantly lower Limb Idleness Index than the control group (p=0.047, Mann–Whitney U test). At 5 weeks post-treatment, microcomputed tomography analysis revealed that there was no difference in any parameter between the treatment and control groups (p>0.05, Student t test). Severe OA histopathological changes were found in both groups. The Osteoarthritis Research Society International scores of the treatment and control groups were 20 (range, 20–26) and 20 (range, 9–26), respectively (p=0.382, Mann–Whitney U test). Conclusion: Intra-articular injection of an antioxidant formulation containing quercetin, vitamin C, and deferoxamine did not retard OA progression in advanced-stage OA. Future studies should aim to determine whether giving antioxidants in early OA, with prolonged drug retention, would be effective in retarding OA progression

Optimisation of platelet concentrates therapy: Composition, localisation, and duration of action

Platelet concentrates (PC) generally refers to a group of products that are prepared from autologous blood intended to enhance healing activities. PC therapy is now very popular in treating musculoskeletal injuries; however, inconsistent clinical results urge the need to understand the working mechanism of PC. It is generally believed that the platelet-derived bioactive factors are the active constituents, and their bioavailability in the vicinity of the lesion sites determines the treatment efficacies. Therefore, the composition, localisation, and duration of the action of PC would be key determinants. In this review, we discuss how different preparations and delivery methods of PC would affect the treatment outcomes with respect to clinical evidence about PC therapy for osteoarthritis, tendinopathies, rotator cuff tears, anterior cruciate ligament injuries, and bone fractures. This review can be used as a quick guide for the use of PC therapy and provide insights for the further optimisation of the therapy in the near future