A Novel Ultrasound Method of Evaluating Dynamic Extrusion of Lateral Meniscus in Healthy Population: Different Patterns of Dynamic Extrusion Revealed Between Lateral and Medial Meniscus.

OBJECTIVES: To establish a reliable ultrasound (US) method of evaluating dynamic extrusion of lateral meniscus in healthy population, and to investigate the pattern of dynamic meniscus extrusion (ME) in lateral meniscus under loading conditions. METHODS: The lateral ME was examined via US method in unloaded, double-leg standing, and single-leg standing positions. Two different US measurement methods were compared to the magnetic resonance imaging (MRI) results to determine the optimal measurement methods. The US results obtained by different researchers were tested for interobserver consistency and the results obtained by the same researcher on two separate days were tested for intraobserver consistency. The patterns of dynamic extrusion were compared between medial and lateral sides. RESULTS: A total of healthy 44 volunteers were included in the study, with 86 knees assessed by US, and 25 knees evaluated by MRI. The US evaluation of dynamic lateral ME demonstrated excellent interobserver and intraobserver reliability. The US measurements using method A were consistent with the MRI results with no significant difference (P = .861, intraclass correlation coefficient [ICC] = 0.868), while method B underestimated the lateral ME compared to MRI (P = .001, ICC = 0.649). Lateral ME decreased slightly from unloaded (1.0 ± 0.8 mm) to single-leg standing position (0.8 ± 0.8 mm), whereas medial ME increased significantly in both double-leg and single-leg standing positions (2.4 ± 0.7 mm, 2.6 ± 0.7 mm). CONCLUSION: A novel US evaluation method of lateral ME was established with reliable and accurate results compared to the MRI. Lateral ME in healthy populations decreased slightly as the loadings increased, which was different from the pattern of dynamic extrusion in medial meniscus.

Medial Cystic Osteochondral Lesions of the Talus Exhibited Lower Sports Levels, Higher Cyst Presence Rate, and Inferior Radiological Outcomes Compared With Lateral Lesions Following Arthroscopic Bone Marrow Stimulation.

PURPOSE: To compare the patient-reported outcomes and radiologic outcomes of the patients with medial and lateral cystic osteochondral lesions of the talus (OLTs) following bone marrow stimulation (BMS). METHODS: Patients with cystic OLTs who underwent BMS between January 2016 and February 2021 were retrospectively analyzed, and the minimum follow-up time was more than 24 months. Patients were paired in a 1:1 ratio (medial cystic OLT [MC-OLT]/lateral cystic OLT [LC-OLT]) based on the OLT area within 30 mm2, follow-up within 1 year, age within 5 years, and ligament surgery (yes/no). The visual analog scale and Foot and Ankle Ability Measure (FAAM)-Activities of Daily Life and Sports scores were assessed preoperatively and postoperatively. The magnetic resonance observation of cartilage repair tissue scores and presence of cysts after BMS were also evaluated. Additionally, the receiver operating characteristic curve was performed. RESULTS: The matched patients were divided into the MC-OLT (n = 31, 43.35 ± 12.32 months) and LC-OLT groups (n = 31, 43.32 ± 14.88 months, P = .986). Thirty patients of each group achieved a power of 80% and an α = 0.05 in this study. The MC-OLT group showed significantly less improvement in FAAM-Activities of Daily Life and sports scores (P = .034, P < .001, respectively), lower magnetic resonance observation of cartilage repair tissue scores (80.80 ± 11.91 vs 86.00 ± 8.50, P = .010), and higher presence rate of cysts after BMS (45.16% vs 16.12%, P = .013). Regarding FAAM sports scores, the LC-OLT group had significantly more patients exceeding the minimal clinically important difference (80.64% vs 51.61%, P = .031). Furthermore, an OLT depth of 7.23 mm (sensitivity: 78.6%; specificity: 70.6%) might serve as a cutoff value for predicting the presence of cysts in medial cystic OLTs following BMS. CONCLUSIONS: Medial cystic OLTs exhibited markedly lower sports levels, higher cyst presence rate, and inferior radiologic outcomes following BMS than lateral counterparts. Additionally, an OLT depth of 7.23 mm could be the cutoff value for predicting the presence of cysts regarding medial cystic OLTs after BMS. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Modified Arthroscopic Bristow Procedure: Screw Fixation Without Subscapularis Split.

In the presence of bone loss, the Bristow or Latarjet procedure is used to alleviate anterior glenohumeral instability. The techniques have gradually improved under arthroscopy. However, such an arthroscopic procedure has a steep learning curve, lengthy operation time, and considerable risk of complications, inhibiting its rapid development. The current method of modified arthroscopic Bristow procedure with screw fixation without subscapularis split reduces surgical time, reduces the risk of nerve damage consequences, and is simple to apply.

Improved indicators of hydrological alteration for quantifying the dam-induced impacts on flow regimes in small and medium-sized rivers.

Dam construction is the main factor altering the flow regimes, while few studies have described that in small and medium-sized rivers (SMRs). The universal indicators of hydrological alteration (IHA) that are widely used in large rivers calculate the parameters just on the annual scale and omit the intra-annual seasonal differences of the flow regimes in SMRs. To fully quantify dam-induced impacts on the flow regimes in SMRs, this paper proposes the improved IHA (IIHA) based on the universal IHA. Then two methods of range of variable approach (RVA) and histogram matching approach (HMA) are used to assess the flow regime alteration. Finally, two indicators of water quantity level (WQL)/hydrological alteration (HA) defined by the parameters in IIHA are employed to evaluate the influence of flow regime alteration on the riverine ecosystem. The case study of a typical SMR named Liujiaping River in Hunan Province, China, verifies the necessity of improving IHA where more hydrological parameters calculated in different periods can comprehensively reflect the flow regime alteration. We find that the integrated hydrological alteration of Liujiaping River assessed by RVA and HMA are both at a high level, and the flow regimes have been significantly altered after the dam construction. Also, the indicators of WQL and HA have higher correlation coefficients with 77 of IIHA parameters and thus can retain as much information of the flow regimes as possible to evaluate the influence of its alteration on the riverine ecosystem.

Outcomes in Patients with Global Pincer Versus Focal Pincer Femoroacetabular Impingement Treated with Hip Arthroscopy: A Retrospective Study with a Minimum 2-Year Follow-Up.

OBJECTIVE: Global pincer is a relatively rare form of pincer deformity and is typically associated with technical challenges during surgery. So far, controversy remains whether patients with global pincer have equivalent surgical outcomes compared to patients with focal pincer. This study compares the clinical outcomes of arthroscopic treatment between patients with global pincer femoroacetabular impingement (FAI) and focal pincer FAI in the Chinese population. METHODS: Data were retrospectively collected from patients with global and focal pincer FAI who underwent hip arthroscopy with a minimum two-year follow-up between April 2016 and December 2018. Radiographic measurements, arthroscopic procedures, preoperative and postoperative patient-reported outcomes (PROs) including modified Harris hip score (mHHS), hip outcome score-activities of daily living (HOS-ADL), international hip outcome tool-12 (iHOT-12), and visual analogue scale (VAS) scores, rates of revision surgery and conversion to total hip arthroplasty (THA) were recorded. Achievement of minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) was compared for the VAS, mHHS, HOS-ADL, and iHOT-12 scores between groups. RESULTS: The total of 33 and 167 patients were included in the global and focal group, respectively. There were no intergroup differences in age, gender, body mass index or follow-up times. Lateral center-edge angle (LCEA) was reduced in both groups postoperatively. Both groups demonstrated significant improvements in PROs compared with preoperative levels at the final follow-up. The preoperative scores showed significant differences in terms of mHHS (60.34 vs 62.90, P = 0.031) and HOS-ADL (61.45 vs 64.74, P = 0.022) scores between two groups, and the improvement of HOS-ADL score was significantly higher in global group (P = 0.027). However, the postoperative scores, including VAS, mHHS, HOS-ADL, and iHOT-12 scores, showed no significant differences between two groups. And there were no significant differences in the rate of meeting the PASS and MCID between groups. One (3.0%) in the global group and six (3.6%) patients in the focal group underwent revision arthroscopy respectively, with no significant difference (P = 0.876). There were no conversions to THA in both groups. CONCLUSIONS: Arthroscopic management of global pincer FAI can achieve excellent functional scores at minimum 2-year follow-up. The outcomes were similar to focal pincer FAI patients with a low rate of secondary procedure.

Modified Arthroscopic Latarjet Procedure: Button Fixation Without Splitting of the Subscapularis.

The Latarjet procedure is used for the treatment of anterior glenohumeral instability in the presence of bone loss. One decade after a fully arthroscopic Latarjet procedure was described, this technique has been modified to reduce the risk of complications and improve the fixation method. We aimed to simplify the components of this surgical procedure.

Clinical outcomes after arthroscopic treatment of calcification with surrounding inflammation in the hip labrum.

PURPOSE: The purpose of this study was to investigate the surgical methods and clinical outcomes of arthroscopic treatment of a special type of calcification with surrounding inflammation in the acetabular labrum of the hip, which was temporarily named "calcifying labrumitis". METHODS: From April 2015 to November 2019, a total of seven patients with calcifying labrumitis of the hip who underwent arthroscopic excision of calcified lesions and suture or partial resection of the labrum were included in this study. Radiographs were retrospectively evaluated for morphologic characteristics of calcifying labrumitis. Each patient was assessed by the visual analogue scale (VAS), modified Harris hip score (mHHS), nonarthritic hip score (NAHS) and satisfaction rate before surgery and at the final follow-up evaluation. RESULTS: Seven patients, one male and six females aged 29-48 years, were included in the study; of these patients, three had calcifying labrumitis on the left side and four had calcifying labrumitis on the right side. All patients had hip pain and limited range of motion for a mean of 7.5 ± 3.1 months (range, 3-12 months). The mean follow-up period was 34.9 ± 19.5 months (range, 12-66 months). The lateral central-edge angle (LCEA) was 31.7 ± 3.9° (range, 28.8-36.4°), and the α angle was 41.4 ± 5.3° (range, 33.6-48.2°). None of the patients had cam or pincer lesions. After complete removal of calcified lesions, five patients underwent repair of the labrum with a suture anchor, and two patients underwent partial resection of the labrum. The symptoms of all patients improved significantly at the last follow-up. Mean scores improved from 5.8 ± 1.5 to 1.1 ± 0.3 (p < 0.01) for the VAS, from 57.3 ± 10.6 to 90.8 ± 13.4 for the mHHS and from 62.5 ± 10.7 to 84.3 ± 9.6 for the NAHS. The satisfaction rate was 100%. CONCLUSION: Calcifying labrumitis of the hip is a special kind of rare disease that is different from calcifications accompanying FAI and os acetabuli. Arthroscopic treatment of calcification with suture or partial resection of the labrum is an effective, safe and minimally invasive method, significantly relieving pain and improving hip joint function. LEVEL OF EVIDENCE: Level IV.

Arthroscopic Excision of Intra-Articular Osteoid Osteoma of the Hip: A Case Series.

PURPOSE: To identify the clinical features of intra-articular osteoid osteoma (OO) of the hip, to evaluate the clinical effect of arthroscopic excision for intra-articular OO, and to summarize the characteristics of revision cases of hip OO and the revision surgery under arthroscopy in these cases. METHODS: We retrospectively reviewed the data of 25 patients who underwent arthroscopic excision of hip OO. The case series included 10 patients who underwent revision surgery. Lesion location, presenting symptoms, and symptom duration were analyzed; postoperative improvement was assessed using the modified Harris Hip Score (mHHS) and International Hip Outcomes Tool (iHot-12) score. We examined the reasons for revision surgery and the characteristics of OO progression after the first surgery. RESULTS: The most common presenting symptom was groin pain that was relieved by nonsteroidal anti-inflammatory drugs (NSAIDs). Varying degrees of limitation of range of motion (ROM) were present in all patients. The osteosclerosis around the tumor nest on computed tomography (CT) scan is a characteristic radiographic feature in this disease. However, the classic radiographic feature was apparent on plain x-rays in only 2 of 25 patients. As a kind of efficient radiological method, magnetic resonance imaging (MRI) can help in distinguishing OO from femoroacetabular impingement (FAI), as the latter is characterized by a large effusion and bone marrow edema at the atypical site of impingement. For the patients who had only 1 arthroscopic resection, the mean (± standard deviation) mHHS and iHot-12 scores were 70.30 ± 9.06 (range 51 to 86) and 75.07 ± 7.69 (57 to 88), respectively. At last follow-up, the mean scores were 98.30 ± 2.15 (94 to 100) and 97.76 ± 2.04 (94 to 100). For revision cases, the mean mHHS and iHot-12 scores were 68.55 ± 3.77 (60 to 72) and 67.88 ± 5.39 (56 to 76). At last follow-up, the mean scores were 97.11 ± 2.47 (94 to 100) and 95.22 ± 1.78 (94 to 100). In the present study, 24 of 25 patients (96%) reached the minimal clinically important difference (MCID) of mHHS, and 21 of 22 patients (95.2%) reached the MCID of iHot-12. Among the revision patients, the most common misdiagnosis at first surgery was FAI. Another feature is that a wrong diagnosis or incomplete intra-articular OO resection can stimulate the tumor and cause an inflammatory reaction and rapidly progressive OA, necessitating prompt revision surgery for complete removal. The degree of joint degeneration was related to the time since the first operation. CONCLUSION: OO of the hip joint typically presents with pain and limited joint activity. Misdiagnosis as FAI or synovitis is common, and CT scan is very helpful for accuracy diagnosis. Arthroscopic excision appears to be an effective method for the treatment of OO of the hip joint. LEVEL OF EVIDENCE: IV, case series.

One-step strategy for cartilage repair using acellular bone matrix scaffold based in situ tissue engineering technique in a preclinical minipig model.

Cartilage defects are most commonly seen in the knee joint. However, due to the limited self-recovery ability of cartilage, the repair of articular cartilage defects is still a great challenge despite that various approaches have been proposed. We designed a strategy to induce cartilage repair using acellular bone matrix (ABM), thereby creating an appropriate microenvironment for the in-situ cells with an easy surgical application. An in vitro system demonstrated that the ABM scaffold could promote cell adhesion, growth, proliferation, and chondrogenesis of mesenchymal stem cells. This experiment was performed in a minipig cartilage repair model. The repaired tissue was hyaline-like cartilage according to the morphological and histological results. The mechanical properties of the repaired tissue were similar to those of normal cartilage. The integration of repaired tissue and normal tissue in the ABM+M group was better than those of other two groups. The ABM-based, one-stage, minimally invasive, in situ procedure for cartilage regeneration can potentially improve the treatment of articular cartilage defects.

Heterotopic ossification after arthroscopy for hip impingement syndrome.

BACKGROUND: Heterotopic ossification (HO) is a known complication of hip arthroscopy. We investigated incidence of HO after hip arthroscopy and determined whether revision for HO improved outcome. METHODS: A retrospective study was conducted on 242 patients (140 men and 102 women, mean age: 36.2 ±â€Š9.5 years) who underwent hip arthroscopy for femoroacetabular impingement (FAI) between January 2016 and January 2018. The average follow-up period was 22.88 ±â€Š11.74 months (range: 11-34 months). Thirteen (5.37%) cases of HO (six men and seven women, five left hips and eight right hips; mean age: 37.5 ±â€Š4.7 years) were observed. Among them, four cases with HO with obvious pain symptoms and persistent non-remission underwent revision surgery to remove HO. Monthly follow-up was conducted. Visual analog scale (VAS), modified Harris Hip Score (mHHS), and non-Arthritis Hip Score (NAHS) were evaluated and compared between HO and non-HO patients. Independent sample t test, Mann-Whitney U test and the Chi-square test were used for inter-group comparisons. HO degree was evaluated using Brooker classification. Symptoms and function were evaluated before and after revision. RESULTS: A total of 242 patients were involved in this study. Thirteen cases (5.4%) had imaging evidence of HO. Nine (9/13) were classified as Brooker stage I, three (3/13) Brooker stage II, and one (1/13) Brooker stage III. HO was detected by ultrasonography as early as 3 weeks after operation. After primary surgery, the mHHS of the HO group and non-HO group increased by 13.00 (8.50, 25.50) and 24.00 (14.00, 34.50) points (Z = -1.80, P = 0.08), NAHS increased by 18.00 (9.50, 31.50) and 26.00 (13.50, 36.00) points (Z = -1.34, P = 0.18), and VAS decreased by 3.00 (2.00, 4.00) and 4.00 (3.00, 4.50) points (Z = -1.55, P = 0.12). Average follow-up time after revision was 9.00 ±â€Š2.94 months; mHHS increased by 34.75 points (t = -55.23, P < 0.01) and NAHS by 28.75 points (t = -6.03, P < 0.01), and VAS decreased by 4 points (t = 9.80, P < 0.01). HO and non-HO patients were similar for demographic and surgical data, and clinical and functional scores. CONCLUSION: HO incidence after arthroscopic treatment of FAI is similar to that found in previous studies. Most HO have no effect on clinical symptoms. Patients who undergo revision HO resection show improvement in pain and joint function.

CaAlg hydrogel containing bone morphogenetic protein 4-enhanced adipose-derived stem cells combined with osteochondral mosaicplasty facilitated the repair of large osteochondral defects.

PURPOSE: Cartilage repair presents a challenge to clinicians and researchers. A more effective procedure that can produce hyaline-like cartilage is needed for articular cartilage repair. Mosaic osteochondral grafts for large osteochondral defects often show poor integration between the grafts and the surrounding normal cartilage, leading to defective cracks filled with fibrous tissue instead of hyaline-like cartilage. In the present study, we aimed to repair the defective cracks with a calcium alginate (CaAlg) hydrogel containing bone morphogenetic protein 4 (BMP4)-enhanced adipose-derived stem cells (ADSCs). METHODS: ADSCs were transduced with BMP4 (B-ADSCs). The expression of BMP4 and type II collagen was confirmed using an enzyme-linked immunosorbent assay (ELISA). Swine models of large cartilage defects of the knee were constructed and received one of the four treatments: mosaicplasty only, mosaicplasty with the CaAlg hydrogel, mosaicplasty with the CaAlg hydrogel containing ADSCs, or mosaicplasty with the CaAlg hydrogel containing B-ADSCs injected into the defective cracks. Outcomes were evaluated at 12 and 24 weeks after surgery. RESULTS: The in vitro study showed that the osteogenic and chondrogenic activities of the B-ADSCs were enhanced compared with those of the control. In vivo, in the group that received mosaicplasty-containing B-ADSCs, osteochondral tissue was completely integrated with an intact surface. Additionally, the histological scores of the mosaicplasty-containing B-ADSCs group were significantly higher than those of the other groups. Biomechanical examination confirmed that the neocartilage possessed properties similar to those of normal cartilage. CONCLUSIONS: Mosaicplasty and hydrogel containing B-ADSCs promoted the repair of large cartilage defects by regenerating hyaline cartilage and repairing dead spaces between osteochondral grafts and donor-site defects, thus improving the feasibility and success rate of one-stage complete repair surgery for large osteochondral defects. This proposed method provides a novel and effective means for the repair of large articular osteochondral defects.

Codelivery of Synovium-Derived Mesenchymal Stem Cells and TGF-ß by a Hybrid Scaffold for Cartilage Regeneration.

Synovium-derived mesenchymal stem cells (SMSCs) are attractive tissue-specific cells for cartilage regeneration because of their easy availability, higher chondrogenic potential, and joint specificity. In the present study, we established a hybrid scaffold to codeliver SMSCs and transforming growth factor beta (TGF-ß), which can integrate the scaffolds, the growth factor, and the autogenous cells within rabbit cartilage defects. A chitosan hydrogel and a decellularized bone matrix were used to fabricate the gel-solid duplex phase biomaterials, which were proven to retain more cells, promote tissue integration, and provide mechanical support. In vitro experiments demonstrated that this hybrid scaffold could release TGF-ß in a controlled biphasic pattern, which can promote cell proliferation and chondrogenic differentiation of loaded rabbit SMSCs. For in vivo experiments, we filled cartilage defects with the hybrid materials, delivering autogenous SMSCs and TGF-ß simultaneously via chitosan's sol-gel transition. Histological analysis, magnetic resonance imaging, and nanoindentation assessment indicated superior cartilage regeneration using this codelivery system compared with that from routine microfracture or control delivery scaffolds. Beyond cartilage regeneration, the easy preparation, favorable biophysical properties, and controlled release ability make this codelivery system applicable to transport other tissue-specific cells or biofactors for tissue engineering.

A co-culture system of rat synovial stem cells and meniscus cells promotes cell proliferation and differentiation as compared to mono-culture.

A meniscus tear often happens during active sports. It needs to be repaired or replaced surgically to avoid further damage to the articular cartilage. To address the shortage of autologous meniscal cells, we designed a co-culture system of synovial stem cells (SMSCs) and meniscal cells (MCs) to produce a large cell number and to maintain characteristics of MCs. Different ratios of SMSCs and MCs at 3:1, 1:1, and 1:3 were tested. Mono-culture of SMSCs or MCs served as control groups. Proliferation and differentiation abilities were compared. The expression of extracellular matrix (ECM) genes in MCs was assessed using an ECM array to reveal the mechanism at the gene level. The co-culture system of SMSCs/MCs at the ratio of 1:3 showed better results than the control groups or those at other ratios. This co-culture system may be a promising strategy for meniscus repair with tissue engineering.

The potential of using semitendinosus tendon as autograft in rabbit meniscus reconstruction.

Since transplantation of meniscal allograft or artificial menisci is limited by graft sources and a series of adverse events, substitution for meniscus reconstruction still needs to be explored. Natural biomaterials, which can provide a unique 3-D microenvironment, remain a promising alternative for tissue engineering. Among them, autograft is a preferred option for its safety and excellent biocompatibility. In this study, we utilized semitendinosus tendon autograft in meniscus reconstruction to investigate its fibrochondrogenic metaplasticity potential and chondroprotective effect. Tendon-derived stem cells (TDSCs) and synovial-derived mesenchymal stem cells (SMSCs), two most important stem cell sources in our strategy, exhibited excellent viability, distribution, proliferation and fibrochondrogenic differentiation ability in decellularized semitendinosus tendon (DST) scaffolds in vitro. Histologic evaluation of the tendon grafts in vivo suggested endogenous stem cells differentiated into fibrochondrocytes, synthesized proteoglycan, type II collagen and radial type I collagen at 12 weeks and 24 weeks post-surgery. As for elastic modulus and hardness of the grafts, there were no significant differences between native meniscus and regenerated meniscus at 24 weeks. The protection of condylar cartilage from degeneration was significantly better in the reconstruction group comparing to control group. Overall, semitendinosus tendon autograft seems to be a promising substitution in meniscus reconstruction.

Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury.

Cartilage tissue engineering is the hotspot of cartilage repair. The allogenic chondrocytes appear to be a promising source of seed cells in cartilage tissue engineering. In this study, we aimed to transplant allogenic chondrocytes with chitosan hydrogel (CS)-demineralized bone matrix (DBM) hybrid scaffold (CS/DBM) to repair rabbit cartilage injury with one-step operation. After the CS/DBM scaffold was successfully fabricated, it showed that the porous CS filled the large pores of DBM, which improved the distribution of seed cells in the CS/DBM scaffold. The allogenic chondrocytes at second passage were transplanted with different scaffolds to repair rabbit cartilage injury. Twenty-four weeks after surgery, the cartilage defect in the CS/DBM group was successfully filled as shown by MRI. Moreover, the histological score of CS/DBM group was significantly higher than that of the other groups. On the aspect of biomechanical property, the regenerated cartilage in the CS/DBM group were superior to those in the other groups as determined by nanoindentation. Meanwhile, no obvious inflammatory response was observed after the transplantation of allogenic chondrocytes at 24 weeks post-surgery. Furtherly, gene expression profile for cells within the repair tissue was compared with the allogenic chondrocytes before transplantation using Agilent microarray and RT-qPCR. The results showed that some genes beneficial to cartilage regeneration, such as BMP-7, HGF, and IGF-1, were upregulated one month after transplantation. Consequently, our study demonstrated that the transplantation of allogenic chondrocytes with CS/DBM scaffold successfully repaired rabbit cartilage injury with only one-step operation, thereby providing new insights into cartilage tissue engineering.

Inhibition of transforming growth factor ß-activated kinase 1 prevents inflammation-related cartilage degradation in osteoarthritis.

Osteoarthritis (OA) is a common debilitating joint disorder, there's still no available disease-modifying drug for OA currently. This study aims to explore the role of TAK1 in OA pathogenesis and therapeutic efficiency of TAK1 inhibition for OA. The contribution of TAK1 to OA pathogenesis was investigated by intra-articular injection of TAK1-encoding adenovirus in rats. TAK1 inhibitor 5Z-7-induced expression changes of extracellular matrix (ECM)-related genes were detected by real-time PCR. The protective effect of 5Z-7 against OA progression was evaluated in a post-traumatic OA rat model. Our results showed that intra-articular injection of Ad-Tak1 induced cartilage destruction and OA-related cytokine secretion in rat joints. TAK1 inhibition by 5Z-7 efficiently blocked NF-κB, JNK and p38 pathways activation in OA chondrocytes and synoviocytes, Meanwhile, 5Z-7 significantly decreased the expression of matrix-degrading enzymes and pro-inflammatory cytokine, while increased ECM protein expression, which are all crucial components in OA. 5Z-7 also ameliorated ECM loss in OA cartilage explants. More importantly, 5Z-7 significantly protected against cartilage destruction in a rat model of OA. In conclusion, our findings provide the first in vivo evidence that TAK1 contributes to OA by disrupting cartilage homeostasis, thus represents an ideal target for OA treatment, with 5Z-7 as a candidate therapeutic.

The TMSB4 Pseudogene LncRNA Functions as a Competing Endogenous RNA to Promote Cartilage Degradation in Human Osteoarthritis.

Mechanical stress plays a key role in the development of cartilage degradation in osteoarthritis (OA). Nevertheless, the role of long noncoding RNAs in mechanical stress-induced regulation of chondrocytes remains unclear. The aim of this study was to explore the function of mechanical stress-related long noncoding RNAs in cartilage. Tissue samples were collected from 50 patients and chondrocytes were exposed to cyclic tensile strain (CTS). A total of 107 lncRNAs were differentially expressed in damaged cartilage versus intact cartilage. Of these lncRNAs, 51 were upregulated and 56 were downregulated in the damaged tissue. The TMSB4 pseudogene, lncRNA-MSR, was upregulated in the damaged cartilage and was activated in chondrocytes in response to mechanical stress. Furthermore, lncRNA-MSR regulated the expression of TMSB4 by competing with miRNA-152 in chondrocytes. Our results demonstrated that upregulation of lncRNA-MSR initiates pathological changes that lead to cartilage degradation, and the inhibition of lncRNA-MSR could represent a potential therapeutic target for OA.

Circular RNA Related to the Chondrocyte ECM Regulates MMP13 Expression by Functioning as a MiR-136 'Sponge' in Human Cartilage Degradation.

Circular RNAs (circRNAs) are involved in the development of various diseases, but there is little knowledge of circRNAs in osteoarthritis (OA). The aim of study was to identify circRNA expression in articular cartilage and to explore the function of chondrocyte extracellular matrix (ECM)-related circRNAs (circRNA-CER) in cartilage. To identify circRNAs that are specifically expressed in cartilage, we compared the expression of circRNAs in OA cartilage with that in normal cartilage. Bioinformatics was employed to predict the interaction of circRNAs and mRNAs in cartilage. Loss-of-function and rescue experiments for circRNA-CER were performed in vitro. A total of 71 circRNAs were differentially expressed in OA and normal cartilage. CircRNA-CER expression increased with interleukin-1 and tumor necrosis factor levels in chondrocytes. Silencing of circRNA-CER using small interfering RNA suppressed MMP13 expression and increased ECM formation. CircRNA-CER could compete for miR-136 with MMP13. Our results demonstrated that circRNA-CER regulated MMP13 expression by functioning as a competing endogenous RNA (ceRNA) and participated in the process of chondrocyte ECM degradation. We propose that circRNA-CER could be used as a potential target in OA therapy.

Runx2-Modified Adipose-Derived Stem Cells Promote Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction.

Runx2 is a powerful osteo-inductive factor and adipose-derived stem cells (ADSCs) are multipotent. However, it is unknown whether Runx2-overexpressing ADSCs (Runx2-ADSCs) could promote anterior cruciate ligament (ACL) reconstruction. We evaluated the effect of Runx2-ADSCs on ACL reconstruction in vitro and in vivo. mRNA expressions of osteocalcin (OCN), bone sialoprotein (BSP) and collagen I (COLI) increased over time in Runx2-ADSCs. Runx2 overexpression inhibited LPL and PPARγ mRNA expressions. Runx2 induced alkaline phosphatase activity markedly. In nude mice injected with Runx2-ADSCs, promoted bone formation was detected by X-rays 8 weeks after injection. The healing of tendon-to-bone in a rabbit model of ACL reconstruction treated with Runx2-ADSCs, fibrin glue only and an RNAi targeting Runx2, was evaluated with CT 3D reconstruction, histological analysis and biomechanical methods. CT showed a greater degree of new bone formation around the bone tunnel in the group treated with Runx2-ADSCs compared with the fibrin glue group and RNAi Runx2 group. Histology showed that treatment with Runx2-ADSCs led to a rapid and significant increase at the tendon-to-bone compared with the control groups. Biomechanical tests demonstrated higher tendon pullout strength in the Runx2-ADSCs group at early time points. The healing of the attachment in ACL reconstruction was enhanced by Runx2-ADSCs.

A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration.

Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.