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Bone & Joint Open
Vol. 5, Issue 9 | Pages 749 - 757
12 Sep 2024
Hajialiloo Sami S Kargar Shooroki K Ammar W Nahvizadeh S Mohammadi M Dehghani R Toloue B

Aims. The ulna is an extremely rare location for primary bone tumours of the elbow in paediatrics. Although several reconstruction options are available, the optimal reconstruction method is still unknown due to the rarity of proximal ulna tumours. In this study, we report the outcomes of osteoarticular ulna allograft for the reconstruction of proximal ulna tumours. Methods. Medical profiles of 13 patients, who between March 2004 and November 2021 underwent osteoarticular ulna allograft reconstruction after the resection of the proximal ulna tumour, were retrospectively reviewed. The outcomes were measured clinically by the assessment of elbow range of motion (ROM), stability, and function, and radiologically by the assessment of allograft-host junction union, recurrence, and joint degeneration. The elbow function was assessed objectively by the Musculoskeletal Tumor Society (MSTS) score and subjectively by the Toronto Extremity Salvage Score (TESS) and Mayo Elbow Performance Score (MEPS) questionnaire. Results. The mean follow-up of patients was 60.3 months (SD 28.5). The mean elbow flexion-extension ROM was 95.8° (SD 21). The mean MSTS of the patients was 84.4 (SD 8.2), the mean TESS was 83.8 (SD 6.7), and the mean MEPS was 79.2 (SD 11.5). All the patients had radiological union at the osteotomy site. Symptomatic osteoarthritic change was observed in three patients (23%), one of whom ended up with elbow joint fusion. Two patients (15.4%) had recurrence during the follow-up period. Surgical complications included two allograft fractures, two plate fractures, three medial instabilities, and two infections. Conclusion. Osteoarticular ulna allograft reconstruction provides acceptable functional outcomes. Despite a high rate of complications, it is still a valuable reconstruction method, particularly in skeletally immature patients who need their distal humerus physis for the rest of hand growth. Cite this article: Bone Jt Open 2024;5(9):749–757


The Bone & Joint Journal
Vol. 106-B, Issue 8 | Pages 783 - 791
1 Aug 2024
Tanaka S Fujii M Kawano S Ueno M Nagamine S Mawatari M

Aims

The aim of this study was to determine the clinical outcomes and factors contributing to failure of transposition osteotomy of the acetabulum (TOA), a type of spherical periacetabular osteotomy, for advanced osteoarthritis secondary to hip dysplasia.

Methods

We reviewed patients with Tönnis grade 2 osteoarthritis secondary to hip dysplasia who underwent TOA between November 1998 and December 2019. Patient demographic details, osteotomy-related complications, and the modified Harris Hip Score (mHHS) were obtained via medical notes review. Radiological indicators of hip dysplasia were assessed using preoperative and postoperative radiographs. The cumulative probability of TOA failure (progression to Tönnis grade 3 or conversion to total hip arthroplasty) was estimated using the Kaplan-Meier product-limited method. A multivariate Cox proportional hazards model was used to identify predictors of failure.


Bone & Joint 360
Vol. 12, Issue 2 | Pages 19 - 24
1 Apr 2023

The April 2023 Foot & Ankle Roundup360 looks at: Outcomes following a two-stage revision total ankle arthroplasty for periprosthetic joint infection; Temporary bridge plate fixation and joint motion after an unstable Lisfranc injury; Outcomes of fusion in type II os naviculare; Total ankle arthroplasty versus arthrodesis for end-stage ankle osteoarthritis; Normal saline for plantar fasciitis: placebo or therapeutic?; Distraction arthroplasty for ankle osteoarthritis: does it work?; Let there be movement: ankle arthroplasty after previous fusion; Morbidity and mortality after diabetic Charcot foot arthropathy.


Bone & Joint Open
Vol. 5, Issue 3 | Pages 227 - 235
18 Mar 2024
Su Y Wang Y Fang C Tu Y Chang C Kuan F Hsu K Shih C

Aims

The optimal management of posterior malleolar ankle fractures, a prevalent type of ankle trauma, is essential for improved prognosis. However, there remains a debate over the most effective surgical approach, particularly between screw and plate fixation methods. This study aims to investigate the differences in outcomes associated with these fixation techniques.

Methods

We conducted a comprehensive review of clinical trials comparing anteroposterior (A-P) screws, posteroanterior (P-A) screws, and plate fixation. Two investigators validated the data sourced from multiple databases (MEDLINE, EMBASE, and Web of Science). Following PRISMA guidelines, we carried out a network meta-analysis (NMA) using visual analogue scale and American Orthopaedic Foot and Ankle Score (AOFAS) as primary outcomes. Secondary outcomes included range of motion limitations, radiological outcomes, and complication rates.


Bone & Joint Research
Vol. 12, Issue 12 | Pages 734 - 746
12 Dec 2023
Chen M Hu C Hsu Y Lin Y Chen K Ueng SWN Chang Y

Aims

Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown.

Methods

We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators.


The Bone & Joint Journal
Vol. 104-B, Issue 10 | Pages 1174 - 1179
1 Oct 2022
Jamshidi K Bagherifard A Mirzaei A

Aims. Osteoarticular reconstruction of the distal femur in childhood has the advantage of preserving the tibial physis. However, due to the small size of the distal femur, matching the host bone with an osteoarticular allograft is challenging. In this study, we compared the outcomes and complications of a resurfaced allograft-prosthesis composite (rAPC) with those of an osteoarticular allograft to reconstruct the distal femur in children. Methods. A retrospective analysis of 33 skeletally immature children with a malignant tumour of the distal femur, who underwent resection and reconstruction with a rAPC (n = 15) or osteoarticular allograft (n = 18), was conducted. The median age of the patients was ten years (interquartile range (IQR) 9 to 11) in the osteoarticular allograft group and nine years (IQR 8 to 10) in the rAPC group (p = 0.781). The median follow-up of the patients was seven years (IQR 4 to 8) in the osteoarticular allograft group and six years (IQR 3 to 7) in the rAPC group (p = 0.483). Limb function was evaluated using the Musculoskeletal Tumor Society (MSTS) score. Results. At final follow-up, the knee was unstable in 9/18 patients (50%) in the osteoarticular allograft group and 2/15 patients (13%) in the rAPC group (p = 0.026). The median range of motion (ROM) of the knee was 117° (IQR 115° to 120°) in the osteoarticular allograft group and 100° (IQR 95° to 105°) in the rAPC group (p < 0.001). The median MSTS score was 25 (IQR 23 to 26) in the osteoarticular allograft group and 28 (IQR 26 to 29) in the rAPC group (p = 0.007). Osteoarthritic change was detected in 11/18 patients (61%) in the osteoarticular allograft group and in 4/15 (26%) patients in the rAPC group (p = 0.048). Conclusion. In our series, a resurfaced allograft-prosthesis composite provided better knee stability and function, with a lower rate of osteoarthritis; an osteoarticular allograft was associated with better knee ROM. Cite this article: Bone Joint J 2022;104-B(10):1174–1179


Bone & Joint Research
Vol. 12, Issue 10 | Pages 615 - 623
3 Oct 2023
Helwa-Shalom O Saba F Spitzer E Hanhan S Goren K Markowitz SI Shilo D Khaimov N Gellman YN Deutsch D Blumenfeld A Nevo H Haze A

Aims. Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model. Methods. A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM. +. ) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM. +. using immunohistochemistry and immunofluorescence. Results. A total of 12 weeks after treatment, 0.5 μg/μl rHAM. +. brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment. Conclusion. We found that 0.5 μg/μl rHAM. +. induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment. Cite this article: Bone Joint Res 2023;12(10):615–623


The Bone & Joint Journal
Vol. 101-B, Issue 7 | Pages 824 - 831
1 Jul 2019
Mahmoud EE Adachi N Mawas AS Deie M Ochi M

Aim. Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. Materials and Methods. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 10. 6. MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II. Results. Within the PBS injection (control group), typical progressive degenerative changes were revealed in the various knee structures. In the single MSC injection (single group), osteoarthritic changes were attenuated, but still appeared, especially in the medial compartments involving fibrillation of the articular cartilage, osteophyte formation in the medial plateau, and longitudinal tear of the meniscus. In the multiple-injections group, the smoothness and texture of the articular cartilage and meniscus were improved. Histologically, absence or reduction in matrix staining and cellularity were noticeable in the control and single-injection groups, respectively, in contrast to the multiple-injections group, which showed good intensity of matrix staining and chondrocyte distribution in the various cartilage zones. Osteoarthritis Research Society International (OARSI) scoring showed significantly better results in the multiple-injections group than in the other groups. Immunohistochemically, collagen I existed superficially in the medial femoral condyle in the single group, while collagen II was more evident in the multiple-injections group than the single-injection group. Conclusion. A single injection of MSCs was not enough to restore the condition of osteoarthritic joints. This is in contrast to multiple injections of MSCs, which had the ability to replace lost cells, as well as reducing inflammation. Cite this article: Bone Joint J 2019;101-B:824–831


The Bone & Joint Journal
Vol. 100-B, Issue 8 | Pages 1117 - 1124
1 Aug 2018
Eamsobhana P Chalayon O Kaewpornsawan K Ariyawatkul T

Aims. Delayed diagnosis is a well-known complication of a Monteggia fracture-dislocation. If left untreated, the dislocated radial head later becomes symptomatic. The purposes of this study were firstly, to evaluate the clinical and radiological results of open reduction of the radial head and secondly, to identify the factors that may affect the outcome of this procedure. Materials and Methods. This retrospective study evaluated 30 children with a chronic Monteggia lesion. There were 18 boys and 12 girls with a mean age of 7.4 years (4 to 13) at the time of open reduction. The mean interval to surgery, after the initial fracture, was 23.4 months (6 to 120). Clinical grading used a Kim modified elbow score: radiological outcome was recorded. The effect of the patient’s age, gender, duration from initial injury, Bado classification, and annular ligament reconstruction were analyzed. The mean follow-up was 42.2 months (15 to 20). Results. The Kim elbow scores evaluated at the last clinic visit were excellent in 23 patients, good in three, fair in two, and poor in two. A majority of the patients were found to have significant improvement of elbow flexion (p < 0.001). Six met the criteria of a fair radiological outcome; four of these were operated on more than 24 months after the initial injury, and three had surgery after the age of 11. Univariate analysis failed to find any factor that was significantly associated with a fair or poor outcome. Conclusion. Good clinical and radiological outcomes can be expected in most patients. Osteoarthritic changes were associated with age > 11 years and/or a delay of treatment of > 24 months. However, no statistically significant factor could be identified which correlated with an unfavourable outcome. Cite this article: Bone Joint J 2018;100-B:1117–24


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 5 | Pages 647 - 652
1 Jul 2002
Nishimatsu H Iida H Kawanabe K Tamura J Nakamura T

We evaluated the long-term results of a modified Spitzy shelf operation for secondary osteoarthritis in 119 hips with a mean follow-up of 23.8 years. The mean age of the patients at the time of surgery was 25 years. Preoperative osteoarthritic change, the age at operation and shelf height were important factors in determining the outcome. Of the 61 hips in the pre-stage (three) and the initial stage (58) of osteoarthritis, 53 (87%) had good results, compared with only 30 (51%) of 58 hips with advanced osteoarthritis. Of the latter, 72% of those aged less than 25 years had good results compared with only 40% of patients aged over 25 years. The shelf height in the group with good results was significantly lower than in those with poor results. This operation is a safe procedure and indicated for acetabular dysplasia or subluxation of the hip with early osteoarthritic change in patients aged less than 25 years


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 7 | Pages 899 - 905
1 Jul 2008
Dias JJ Dhukaram V Abhinav A Bhowal B Wildin CJ

We report the outcome at a mean of 93 months (73 to 110) of 71 patients with an acute fracture of the scaphoid who were randomised to Herbert screw fixation (35) or below-elbow plaster cast immobilisation (36). These 71 patients represent the majority of a randomised series of 88 patients whose short-term outcome has previously been reported. Those patients available for later review were similar in age, gender and hand dominance. There was no statistical difference in symptoms and disability as assessed by the mean Patient Evaluation Measure (p = 0.4), or mean Patient-Rated Wrist Evaluation (p = 0.9), the mean range of movement of the wrist (p = 0.4), mean grip strength (p = 0.8), or mean pinch strength (p = 0.4). Radiographs were available from the final review for 59 patients. Osteoarthritic changes were seen in the scaphotrapezial and radioscaphoid joints in eight (13.5%) and six patients (10.2%), respectively. Three patients had asymptomatic lucency surrounding the screw. One non-operatively treated patient developed nonunion with avascular necrosis. In five patients who were treated non-operatively (16%) there was an abnormal scapholunate angle ( > 60°), but in four of these patients this finding was asymptomatic. No medium-term difference in function or radiological outcome was identified between the two treatment groups


The Journal of Bone & Joint Surgery British Volume
Vol. 48-B, Issue 1 | Pages 82 - 91
1 Feb 1966
Green JP

1. This is a small series and patients have been treated in a variety of ways. Some impressions emerge, however, concerning the importance of initial trauma, the importance of the factor of heredity and the results of treatment. 2. More than 40 per cent of the patients in the series had an injury to the knee before symptoms began, which tends to support the traumatic theory. Twenty of the twenty-three patients who gave a past history of trauma had a lesion on the medial condyle, next to the intercondylar notch, and one patient of the three who had lesions on the lateral femoral condyle suffered from recurrent dislocation of the patella. 3. Although numerous examples have been reported in the literature of osteochondritis dissecans occurring in several members of a family, the family history of only one patient in this series suggested a familial tendency, and this was doubtful. It seems that patients showing a familial tendency are not commonly seen compared with the number of patients presenting with osteochondritis dissecans. 4. It is often stated that osteoarthritic changes will follow if part of the articular surface is lost, as in osteochondritis dissecans, and this belief has led to the school of thought which advocates restoration of the articular surface by reposition of the fragment. While there is no doubt that this method should be used if a large proportion of the weight-bearing surface of a femoral condyle is affected, the argument has less force if a small area is affected. It is interesting to find that of the five patients treated by replacement of a separated fragment four developed osteoarthritis, whereas in the first series only six patients out of the twenty-two developed such changes. Although these former had what appeared to be an accurate reposition of the fragment it is possible that a "step up" on the joint surface was produced, which gave rise to a more rapid deterioration of the articular cartilage. Accurate conclusions cannot be drawn from five patients, but it may be that attempts to reconstruct the articular surface of a femoral condyle can, over a long period of time, give worse results than simple removal of the lesion. 5. The group of patients treated conservatively gave encouraging results, and improved radiographic appearances were seen in most cases. There was also a notable absence of osteoarthritic changes and these results support the view that conservative treatment is indicated in adolescents and children


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 7 | Pages 911 - 915
1 Jul 2005
van Hellemondt GG Sonneveld H Schreuder MHE Kooijman MAP de Kleuver M

We report the long-term results of 51 pelvic osteotomies in 43 patients with a mean follow-up of 15 years (13 to 20). The mean age of the patients was 28 years (14 to 46). At review three patients were lost to follow-up, and six had received a total hip arthroplasty. Of 48 hips, 42 (88%) were preserved, with good to excellent clinical results in 27 (64%). Pre-operatively, 41 (80%) of the treated hips had shown no sign of osteoarthritis. Thirty-one (65%) hips showed no progression of osteoarthritis after follow-up for 15 years. Significant negative factors for good long-term results were the presence of osteoarthritic changes and a fair or poor clinical score pre-operatively. Pelvic reorientation osteotomy for symptomatic hip dysplasia can give satisfactory and reproducible long-term clinical results


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 743 - 750
1 Jul 2023
Fujii M Kawano S Ueno M Sonohata M Kitajima M Tanaka S Mawatari D Mawatari M

Aims

To clarify the mid-term results of transposition osteotomy of the acetabulum (TOA), a type of spherical periacetabular osteotomy, combined with structural allograft bone grafting for severe hip dysplasia.

Methods

We reviewed patients with severe hip dysplasia, defined as Severin IVb or V (lateral centre-edge angle (LCEA) < 0°), who underwent TOA with a structural bone allograft between 1998 and 2019. A medical chart review was conducted to extract demographic data, complications related to the osteotomy, and modified Harris Hip Score (mHHS). Radiological parameters of hip dysplasia were measured on pre- and postoperative radiographs. The cumulative probability of TOA failure (progression to Tönnis grade 3 or conversion to total hip arthroplasty) was estimated using the Kaplan–Meier product-limited method, and a multivariate Cox proportional hazard model was used to identify predictors for failure.


Bone & Joint 360
Vol. 12, Issue 1 | Pages 42 - 45
1 Feb 2023

The February 2023 Children’s orthopaedics Roundup360 looks at: Trends in management of paediatric distal radius buckle fractures; Pelvic osteotomy in patients with previous sacral-alar-iliac fixation; Sacral-alar-iliac fixation in patients with previous pelvic osteotomy; Idiopathic toe walking: an update on natural history, diagnosis, and treatment; A prediction model for treatment decisions in distal radial physeal injuries: a multicentre retrospective study; Angular deformities after percutaneous epiphysiodesis for leg length discrepancy; MRI assessment of anterior coverage is predictive of future radiological coverage; Predictive scoring for recurrent patellar instability after a first-time patellar dislocation.


Bone & Joint 360
Vol. 13, Issue 1 | Pages 26 - 29
1 Feb 2024

The February 2024 Shoulder & Elbow Roundup360 looks at: Does indomethacin prevent heterotopic ossification following elbow fracture fixation?; Arthroscopic capsular shift in atraumatic shoulder joint instability; Ultrasound-guided lavage with corticosteroid injection versus sham; Combined surgical and exercise-based interventions following primary traumatic anterior shoulder dislocation: a systematic review and meta-analysis; Are vascularized fibula autografts a long-lasting reconstruction after intercalary resection of the humerus for primary bone tumours?; Anatomical versus reverse total shoulder arthroplasty with limited forward elevation; Tension band or plate fixation for simple displaced olecranon fractures?; Is long-term follow-up and monitoring in shoulder and elbow arthroplasty needed?


Bone & Joint 360
Vol. 12, Issue 5 | Pages 27 - 30
1 Oct 2023

The October 2023 Wrist & Hand Roundup360 looks at: Distal radius fracture management: surgeon factors markedly influence decision-making; Fracture-dislocation of the radiocarpal joint: bony and capsuloligamentar management, outcomes, and long-term complications; Exploring the role of artificial intelligence chatbot in the management of scaphoid fractures; Role of ultrasonography for evaluation of nerve recovery in repaired median nerve lacerations; Four weeks versus six weeks of immobilization in a cast following closed reduction for displaced distal radial fractures in adult patients: a multicentre randomized controlled trial; Rehabilitation following flexor tendon injury in Zone 2: a randomized controlled study; On the road again: return to driving following minor hand surgery; Open versus single- or dual-portal endoscopic carpal tunnel release: a meta-analysis of randomized controlled trials.


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 760 - 767
1 Jul 2023
Tanaka S Fujii M Kawano S Ueno M Sonohata M Kitajima M Mawatari D Mawatari M

Aims

The aims of this study were to validate the Forgotten Joint Score-12 (FJS-12) in the postoperative evaluation of periacetabular osteotomy (PAO), identify factors associated with joint awareness after PAO, and determine the FJS-12 threshold for patient-acceptable symptom state (PASS).

Methods

Data from 686 patients (882 hips) with hip dysplasia who underwent transposition osteotomy of the acetabulum, a type of PAO, between 1998 and 2019 were reviewed. After screening the study included 442 patients (582 hips; response rate, 78%). Patients who completed a study questionnaire consisting of the visual analogue scale (VAS) for pain and satisfaction, FJS-12, and Hip disability and Osteoarthritis Outcome Score (HOOS) were included. The ceiling effects, internal consistency, convergent validity, and PASS thresholds of FJS-12 were investigated.


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1399 - 1407
1 Dec 2024
Fujii M Tanaka S Kawano S Ueno M Nagamine S Mawatari M

Aims

This study aimed to determine clinical outcomes; relationships between postoperative anterior, lateral, and posterior acetabular coverage and joint survival; and prognostic factors for joint survival after transposition osteotomy of the acetabulum (TOA).

Methods

Data from 616 patients (800 hips) with hip dysplasia who underwent TOA between November 1998 and December 2019 were reviewed. The median follow-up period was 8.9 years (IQR 5 to 14). A medical notes review was conducted to collect demographic data, complications, and modified Harris Hip Score (mHHS). Radiological indicators of acetabular coverage included lateral centre-edge angle (LCEA), anterior wall index (AWI), and posterior wall index (PWI). The cumulative probability of TOA failure (progression to Tönnis grade 3 or conversion to total hip arthroplasty) was estimated using the Kaplan-Meier product-limited method. A multivariate Cox proportional hazards model was used to identify predictors for failure.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 137 - 148
1 Apr 2024
Lu Y Ho T Huang C Yeh S Chen S Tsao Y

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

Methods

Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers.