Osteochondritis dissecans (OCD) is an acquired, potentially reversible idiopathic disease of subchondral bone resulting in delamination and sequestration. Although juvenile-type OCD lesions typically appear stable on superficial examination, conservative treatment results in cure in approximate 50% of patients. We hypothesized that juvenile-type OCD lesions exhibit an underlying instability despite stability at the articular surface and this underlying instability might underlie the lack of effectiveness of conservative treatment. In this study, osteochondral cylindrical tissue samples obtained from stable juvenile OCD lesions located at the medial femoral condyle (classical site) were examined. Eight patients with symptomatic juvenile-type OCD at the classical site underwent arthroscopy. Osteochondral cylindrical tissue samples were obtained from the central portion using a biopsy needle. The samples underwent macroscopic and microscopic examination. All cylindrical samples demonstrated macroscopic separation. On microscopic examination, no degenerative changes in articular cartilage and no bone necrosis were observed. Histological examination revealed two distinct patterns in the samples: (1) thick homogeneous hyaline cartilage alone with little fibrous tissue surrounding areas of separation and (2) nearly normal, thin hyaline cartilage above a mixed layer of hyaline cartilage and subchondral trabeculae and fibrous/fibro-cartilaginous tissue at the areas of separation, indicating delayed or nonunion. Pathological findings in stable juvenile OCD lesions indicate an underlying instability at deeper layers of articular cartilage and poor healing at areas of separation. Improved knowledge of the histology of juvenile-type OCD lesions may support surgical treatment. Early marrow stimulation and/or fixation may be the treatment of choice to promote healing even in macroscopically stable juvenile-type OCD lesions.

BRCA2 is a tumor suppressor gene that is linked to hereditary breast and ovarian cancer. Although the Brca2 protein participates in homologous DNA recombination (HR), its precise role remains unclear. From chicken DT40 cells, we generated BRCA2 gene-deficient cells which harbor a truncation at the 3 end of the BRC3 repeat (brca2tr). Comparison of the characteristics of brca2tr cells with those of other HR-deficient DT40 clones revealed marked similarities with rad51 paralog mutants (rad51b, rad51c, rad51d, xrcc2, or xrcc3 cells). The phenotypic similarities include a shift from HR-mediated diversification to single-nucleotide substitutions in the immunoglobulin variable gene segment and the partial reversion of this shift by overexpression of Rad51. Although recent evidence supports at least Xrcc3 and Rad51C playing a role late in HR, our data suggest that Brca2 and the Rad51 paralogs may also contribute to HR at the same early step, with their loss resulting in the stimulation of an alternative, error-prone repair pathway.Individuals carrying germ line mutations of the BRCA2 gene have a high risk of developing breast and ovarian cancer (40,45,76). The Brca2 protein acts as a tumor suppressor, and its loss results in genome instability (1,30,35). Mice carrying a deletion of all eight BRC repeats die during early embryonic development, while mice carrying a truncation at the 3Ј end of the third BRC repeat (brca2tr mice) are partially viable (10,13,29,35). However, interpretation of their phenotype may be hampered by additional mutations acquired during the derivation of the line as a result of the genomic instability imposed by impaired Brca2 function.While yeast Rad51, Rad52, and Rad54 contribute to homologous DNA recombination (HR) to similar extents, vertebrate Rad51 plays a dominant role in HR (25,48,57). HR is initiated by polymerization of Rad51 on single-stranded DNA at sites of DNA damage, leading to formation of nucleoprotein filaments (3,33,50,72). The filaments undergo homologous pairing and strand exchange with other intact homologous DNA to form the Holliday junction recombination intermediates, followed by resolution of the two homologous DNAs. It has been suggested that Brca2 may regulate the Rad51 recombinase (30,36,67,70), because the brca2 mutation impairs ionizing radiation (IR)-induced subnuclear Rad51 focus formation (20,58,61,73), which is believed to represent the polymerization of Rad51 at sites of DNA damage (16,27,39,55). However, the biological significance of impaired Rad51 focus formation has not been clarified, because brca2tr cells exhibit only marginal IR sensitivity and thus retain a substantial fraction of the Rad51-dependent capability for repair of IR-induced double strand breaks (DSBs). Furthermore, in mammalian cells, there is neither a detailed phenotypic assay that can address the role of each molecule in the HR reaction nor a collection of HR mutant cell lines with which each phenotype can be accurately compared. Therefore, reverse genetic studies of mammalian cells have g...

Background: Meniscal function after repair of radial/flap tears of the posterior horn of the lateral meniscus (LM) with anterior cruciate ligament reconstruction (ACLR) has not been comprehensively investigated. Purpose: To evaluate not only the clinical and radiographic outcomes of patients with repair of radial/flap tears of the posterior LM with ACLR but also the healing status of the repaired meniscus and changes of chondral status with second-look arthroscopy. Study Design: Case series; Level of evidence, 4. Methods: From January 2008 to April 2016, 41 patients of a consecutive series of 505 primary anatomic ACLR cases had a concomitant radial/flap tear of the posterior horn of the LM and underwent side-to-side repair with an inside-out or all-inside technique. All patients were followed for >2 years, evaluated clinically and radiologically (radiograph and magnetic resonance imaging [MRI]), and compared with a control group without any concomitant injuries that underwent ACLR. Of the 41 patients, 30 were assessed by second-look arthroscopy 2 years postoperatively. Results: The mean follow-up times of the study and control groups were 3.4 and 3.9 years, respectively. The study group showed no significant differences in clinical findings, lateral joint space narrowing on radiograph, and coronal extrusion on MRI as compared with the control group, whereas sagittal extrusion on MRI progressed significantly in the study group (1.2 ± 1.5 mm vs 0.32 ± 1.0 mm, P < .001). Eighteen patients (60%) obtained complete healing; 9 (30%) showed partial healing; and 3 (10%) failed to heal on second-look arthroscopy. Changes of chondral status in the femoral condyle showed no significant difference between the groups ( P = .29). However, chondral status of the lateral tibial plateau worsened significantly in the study group ( P = .0011). Conclusion: The clinical and radiographic outcomes after repair of radial/flap tears of the posterior horn of the LM as combined with anatomic ACLR were successful and comparable with those after isolated ACLR without any other injuries at a mean postoperative follow-up of 3.4 years, except for sagittal extrusion on MRI. Chondral lesions of the lateral tibial plateau deteriorated regardless of meniscal healing at 2 years postoperatively. Surgeons should keep in mind that chondral injuries might progress over the midterm.

Metazoan Rad51 plays a central role in homologous DNA recombination, and its activity is controlled by a number of Rad51 cofactors. These include five Rad51 paralogs, Rad51B, Rad51C, Rad51D, XRCC2 and XRCC3. We previously hypothesized that all five paralogs participate collaboratively in repair. However, this idea was challenged by the biochemical identification of two independent complexes composed of either Rad51B/C/D/XRCC2 or Rad51C/XRCC3. To investigate if this biochemical finding is matched by genetic interactions, we made double mutants in either the same complex (rad51b/rad51d) or in both complexes (xrcc3/rad51d). In agreement with the biochemical findings the double deletion involving both complexes had an additive effect on the sensitivity to camptothecin and cisplatin. The double deletion of genes in the same complex, on the other hand, did not further increase the sensitivity to these agents. Conversely, all mutants tested displayed comparatively mild sensitivity to γ-irradiation and attenuated γ-irradiation-induced Rad51 foci formation. Thus, in accord with our previous conclusion, all paralogs appear to collaboratively facilitate Rad51 action. In conclusion, our detailed genetic study reveals a complex interplay between the five Rad51 paralogs and suggests that some of the Rad51 paralogs can separately operate in later step of homologous recombination.

Autologous scaffold-free TEC derived from synovial MSCs may be used for regenerative cartilage repair via a sutureless and simple implantation procedure. Registration: 000008266 (UMIN Clinical Trials Registry number).