Distinct dysregulation of the small leucine-rich repeat protein family in osteoarthritic acetabular labrum compared to articular cartilage.

OBJECTIVE: Articular cartilage is well studied in osteoarthritis (OA). However, the role of supporting structures, such as the acetabular labrum, a sealing structure surrounding the hip joint, has been investigated much less. We recently showed that fibrochondrocytic labrum cells are metabolically active. This study was undertaken to investigate hip OA­associated changes in human acetabular labrum cells. METHODS: Microarray analysis was performed to compare OA labrum cells to healthy labrum cells cultured in a 3-dimensional alginate bead system. Data were analyzed by cluster analysis using gene set enrichment analysis software and by gene list analysis using PANTHER gene family tools. Selected candidates were validated by quantitative polymerase chain reaction analysis on labrum and cartilage samples and by immunohistochemistry. The functional impacts of the genes identified were investigated by in vitro stimulation experiments in labrum cells. RESULTS: Pathway analysis revealed increased cytokine and chemokine signaling in OA labrum cells, whereas reduced extracellular matrix interactions and transforming growth factor ß signaling were observed. Several genes were significantly differentially expressed in OA compared to healthy labrum. We specifically focused on 3 small leucine-rich repeat proteins (SLRPs), osteomodulin, osteoglycin, and asporin, that appeared to be distinctly regulated in OA labrum compared to OA cartilage. SLRPs were strongly down-regulated in OA labrum but up-regulated in OA articular chondrocytes. Moreover, in vitro stimulation with osteomodulin increased aggrecan expression in OA labrum cells. CONCLUSION: OA labrum fibrochondrocytes have several features similar to OA chondrocytes. However, SLRP expression seems to be differentially influenced by degeneration in OA labrum compared to cartilage, suggesting a specific role for this supporting structure in OA. The functional impact of SLRPs on labrum cells makes them interesting targets for further studies in hip OA.

Constitutional varus does not affect joint line orientation in the coronal plane.

BACKGROUND: In a previous study, we described the distribution of coronal alignment in a normal asymptomatic population and recognized the occurrence of constitutional varus in one of four individuals. It is important to further investigate the influence of this condition on the joint line orientation and how the latter is affected by the onset and progression of arthritis. QUESTIONS/PURPOSES: The purposes of this study are (1) to describe the distribution of joint line orientation in the coronal plane in the normal population; (2) to compare joint line orientation between patients with constitutional varus and neutral mechanical alignment; and (3) to compare joint line orientation between a cohort of patients with prearthritic constitutional varus and a cohort of patients with established symptomatic varus arthritis. METHODS: Full-leg standing hip-to-ankle digital radiographs were performed in 248 young healthy individuals and 532 patients with knee arthritis. Hip-knee-ankle (HKA) angle and tibial joint line angle (TJLA) were measured in the coronal plane. Patients were subdivided into varus (HKA ≤ -3°), neutral, and valgus (HKA ≥ 3°). RESULTS: The mean TJLA in healthy subjects was 0.3° (SD 2.0°). TJLA was parallel to the floor in healthy subgroups with neutral alignment (TJLA 0.3°, SD 1.9) and constitutional varus (TJLA 0.2°, SD 2.2°). In patients with symptomatic arthritis and varus alignment, the TJLA opened medially (mean -1.9°, SD 3.5°). CONCLUSIONS: Constitutional varus does not affect joint line orientation. Advanced medial arthritis causes divergence of the joint line from parallel to the floor. These findings influence decision-making for osteotomy and alignment in total knee arthroplasty.

Histologic assessment of acetabular labrum healing.

PURPOSE: The purpose of this study was to histologically examine the human healing response of arthroscopically repaired acetabular labrum tears. METHODS: Biopsy specimens were retrieved from 6 patients during total hip arthroplasty after clinical failure of the index arthroscopic procedure. All patients were diagnosed as having femoroacetabular impingement with a concomitant labral tear. In all cases severe chondral damage was observed during arthroscopy (Beck grades 3 to 4). Despite successful technical repair of the labral tear, chondral damage in these patients was so advanced that the clinical progress after the procedure was unsatisfactory and arthroplasty of the joint was required. Biopsy specimens of the repaired acetabular labra were harvested during the arthroplasty surgery and processed for standard histologic evaluation. RESULTS: Macroscopically and histologically, all repaired labra kept their triangular shape more or less and appeared to have healed. All harvested biopsy specimens displayed a typical fibrocartilaginous appearance with limited vascular supply. Calcifications were present in only 1 biopsy specimen. In 3 cases neovascularization of the labral tissue was noticed in the proximity of the sutures. In the superficial and deep parts of the labral body, small clefts were observed in all cases. CONCLUSIONS: In this study the histologic aspects of arthroscopically repaired human labral tears were addressed. It was shown that human labral tears show healing potential after surgical repair. The surfaces of the labral tissues were intact, and neither remnants of the tear nor the presence of fibrovascular scar tissue was observed. However, some small clefts in the superior and deep parts of the repaired structures were noticed in all cases. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

The use of scaffolds in the treatment of osteochondral lesions in the knee: current concepts and future trends.

Long after the first reports on human autologous chondrocyte implantation (ACI) by Brittberg in 1994, the development of a so-called optimal technology for osteochondral tissue regeneration is still one of the most challenging issues in knee surgery. Although the short- and intermediate-term results of ACI appear to be favorable, resources are being directed toward scaffold research to improve the technology. Scaffolds used for osteochondral repair may be either cell or noncell-based before its implantation in the knee. The characteristics that make scaffolds optimal for clinical use are that they be biocompatible, biodegradable, permeable, reproducible, mechanically stable, noncytotoxic, and capable of serving as a temporary support for the cells while allowing for eventual replacement by matrix components synthesized by the implanted cells. There is a growing interest in noncell and last-minute cell seeding technologies since they allow for a one-step surgery eliminating the morbidity and necessity of a previous chondral biopsy. Although clinical and histological results from many, already clinically available scaffolds seem to be promising, improvements throughout these technologies and the developments of new ones are still necessary to obtain a more efficient biological response as well as to improve the implant's stability. Moreover, as the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention should be directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only.

Midterm results of the treatment of cartilage defects in the knee using alginate beads containing human mature allogenic chondrocytes.

BACKGROUND: The treatment of chondral lesions is still an important challenge for the orthopaedic surgeon. Attempts have been made to restore cartilage lesions by filling the defects with a temporary biocompatible matrix. PURPOSE: The authors present their midterm experience with the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of cartilage lesions in the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A biodegradable, alginate-based biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of cartilage lesions in the knee. Twenty-one patients were clinically prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a visual analog scale (VAS). The mean follow-up time was 6.3 years (range, 5-8 years). Magnetic resonance imaging (MRI) data were analyzed based on the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) system, allowing morphologic assessment of the repair tissue. Magnetic resonance images were taken at 1 year of follow-up and at a mean follow-up of 6.1 years (range, 5-7 years). RESULTS: During the follow-up period, the WOMAC and VAS scores improved significantly. No signs of clinical deterioration or adverse reactions to the alginate beads/allogenic chondrocyte implantation were observed. Four failures occurred during the follow-up period in this study (19.05%). The MOCART scores were moderate and remained stable in time. CONCLUSION: This investigation provided useful information on the efficacy of the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of cartilage lesions in the knee. The midterm clinical outcome of the presented technique was satisfactory. However, these results were not confirmed by the MRI findings.

A pilot study of the use of an osteochondral scaffold plug for cartilage repair in the knee and how to deal with early clinical failures.

PURPOSE: To present our short-term experience with an osteochondral scaffold plug (TruFit plug; Smith & Nephew, Andover, MA) for cartilage repair in the knee and, more importantly, to discuss our approach to treat early clinical failures. METHODS: Twenty patients were consecutively treated for their cartilage lesions with the plug technique. These patients were prospectively clinically evaluated at 6 and 12 months of follow-up. Magnetic resonance imaging (MRI) was used for morphologic analysis of the cartilage repair. Biopsy samples were taken from 3 cases during revision surgery, allowing histologic assessment of the repair tissue. RESULTS: The short-term clinical and MRI outcome of this pilot study are modest. No signs of deterioration of the repair tissue were observed. Of the 15 patients followed up during 1 year, 3 (20.0%) showed persistent clinical symptoms or even more clinical symptoms after insertion of the plug. These patients were considered as failures and therefore eligible for revision surgery. During revision surgery, the repair tissue was carefully removed. The remaining osteochondral defect was filled with autologous bone grafts. Immediate and persistent relief of symptoms was observed in all 3 patients. Histologic assessment of biopsy specimens taken during revision surgery showed fibrous vascularized repair tissue with the presence of foreign-body giant cells. CONCLUSIONS: The overall short-term clinical and MRI outcome of the osteochondral scaffold plug for cartilage repair in the knee is modest. In this pilot study a modest clinical improvement became apparent at 12 months of follow-up. MRI data showed no deterioration of the repair tissue. Of the 15 patients, 3 (20%) had persistent clinical symptoms after surgery. These patients were successfully treated with removal of the osteochondral plug remnants and the application of autologous bone grafts. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Treatment of cartilage defects in the knee using alginate beads containing human mature allogenic chondrocytes.

BACKGROUND: The repair of osteochondral lesions is imperfect and transient; chondral lesions do not heal in mature cartilage. Attempts have been made to restore cartilage lesions by filling the defects with a temporary artificial biocompatible matrix. PURPOSE: To determine whether the implantation of alginate beads containing human mature allogenic chondrocytes is feasible and safe for the treatment of symptomatic cartilage defects in the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A biodegradable, alginate-based, biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of chondral and osteochondral lesions in the knee. Twenty-one patients were clinically and prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index and a visual analog scale for pain preoperatively and at 3, 6, 9, 12, 18, and 24 months of follow-up. Of the 21 patients, 13 consented to having a biopsy sample taken for investigative purposes from the area of implantation at 12 months of follow-up, allowing histologic assessment of the repair tissue. RESULTS: A statistically significant clinical improvement became apparent after 6 months, and patients improved during the 24 months of follow-up. Adverse reactions to the alginate/fibrin matrix seeded with the allogenic cartilage cells were not observed. Histologic analysis of the biopsy specimens rated the repair tissue as hyaline-like in 15.3% of the samples, as mixed tissue in 46.2%, as fibrocartilage in 30.8%, and as fibrous in 7.7%. CONCLUSION: The results of this short-term pilot study show that the alginate-based scaffold containing human mature allogenic chondrocytes is feasible and safe for the treatment of symptomatic cartilage defects of the knee. The described technique provides clinical and histologic outcomes that are equal but not superior to those of other cartilage repair techniques.