Hasil untuk "Orthopedic surgery"

Ho‐Kwong Li, I. Rombach, R. Zambellas et al.

BACKGROUND The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow‐on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS Among the 1054 participants (527 in each group), end‐point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end‐point data (39 participants, 3.7%) were imputed. The intention‐to‐treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of ‐1.4 percentage points (90% confidence interval [CI], ‐4.9 to 2.2; 95% CI, ‐5.6 to 2.9), indicating noninferiority. Complete‐case, per‐protocol, and sensitivity analyses supported this result. The between‐group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927.)

A. White, M. Panjabi

D. Anderson, G. P. Morgano, C. Bennett et al.

BACKGROUND Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality. OBJECTIVE These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery. METHODS ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2). CONCLUSIONS For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.

D. Docheva, S. Müller, M. Majewski et al.

Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation. Therapeutic options used to repair ruptured tendons have consisted of suture, autografts, allografts, and synthetic prostheses. To date, none of these alternatives has provided a successful long-term solution, and often the restored tendons do not recover their complete strength and functionality. Unfortunately, our understanding of tendon biology lags far behind that of other musculoskeletal tissues, thus impeding the development of new treatment options for tendon conditions. Hence, in this review, after introducing the clinical significance of tendon diseases and the present understanding of tendon biology, we describe and critically assess the current strategies for enhancing tendon repair by biological means. These consist mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage. A deeper understanding of how tendon tissue and cells operate, combined with practical applications of modern molecular and cellular tools could provide the long awaited breakthrough in designing effective tendon-specific therapeutics and overall improvement of tendon disease management.

Yueliang Zhu, Yanli Li, Jian Shi et al.

Purpose: This study aims to investigate the X-ray manifestations of hypotrophic new bone formation in tibial bone transport, propose a classification system, and establish standard treatment protocols. Materials and methods: A retrospective analysis was conducted on 53 out of 378 cases of hypotrophic distraction osteogenesis in tibial bone transport, performed from January 2012 to December 2023. The cohort included 34 males and 19 females, aged 18–71 years (mean age: 37.8 years). Distraction sites comprised 31 cases in the proximal tibia, 7 in the tibial shaft, and 15 in the distal tibia, with defect lengths ranging from 3.3 cm to 22.4 cm (average: 6.3 cm). X-ray imaging categorized hypotrophic bone formation into four types: longitudinal shape (Type A), transverse shape (Type B), worm-bitten shape (Type C), and complete shape (Type D). The treatment protocol included assessment and management of the general condition, callus stimulation through adjustments in transport rate or direction, and surgical interventions. The external fixation index (EFI) assessed healing and mineralization, while limb function was evaluated using the Paley method. Results: Follow-up data over an average of 33.71 ± 11.7 months indicated that 2 cases required amputation, while 51 achieved bone union, restoring mobility in the transported leg. The EFI ranged from 1.47 to 2.73 months/cm, averaging 1.78 ± 0.32 months/cm. Outcomes were classified as excellent in 34 cases, good in 11, fair in 3, and poor in 3, resulting in an overall excellent and good rate of 84.9 %. Conclusion: The X-ray characteristics of hypotrophic bone formation in tibial transport can be effectively categorized. A systematic evaluation followed by tailored interventions leads to favorable treatment outcomes.

Lucas Schreff, Katharina Nirmaier, Christian Blank et al.

<b>Background/Objectives</b>: During adult walking, ground reaction forces (GRFs) consistently intersect near a point above the center of mass (CoM), termed the virtual pivot point (VPP). The VPP is hypothesized to contribute to upper body stabilization. However, little is known about its presence and developmental trajectory during early childhood. This study investigated age-related differences in VPP position, variability, and GRF focusing during walking in typically developing children. <b>Methods</b>: Kinematic and kinetic data were collected from 29 children across three age groups: Group I (aged 1 year), Group II (aged 2–3 years), and Group III (aged 10–15 years) using markerless motion capture and force plates. VPP position relative to the CoM, its variability and GRF focusing (<i>R</i>²) were analyzed in sagittal plane during single support phases. <b>Results</b>: Across all age groups, GRFs were strongly focused toward a VPP (<i>R</i>² > 0.95), with no significant age-related differences in GRF focusing. In contrast, significant age-related differences emerged in VPP position and variability. The normalized vertical VPP position increased progressively from Group I (7.58 cm) to Group III (14.79 cm). Notably, in several toddlers, the VPP was located at or below the CoM, contrasting with the consistent above-CoM position observed in adolescents. <b>Conclusions</b>: These findings demonstrate that while GRF focusing behavior is present in toddlers who can walk independently, VPP characteristics undergo substantial developmental changes. The shifting VPP position and the decrease in variability in toddlers likely reflect progressive changes in gait mechanics and trunk stabilization strategies during childhood.

Remzi Tozun, Ayhan Aritamur, Orhan Baskir et al.

Abstract Discoid meniscus is rare anomaly and usually the clinical re are no findings in childhood. Three cases of discoid meniscus are presented below and its diagnosis and treatment problems discussed under the light of literature. ÖzetNadir görülen bir anomali olan diskoid meniskus, çocukluk çağında genellikle klinik belirti vermez. Bu nedenle çocukluk çağındaki, iki taraflı lateral diskoid meniskuslu 3 olgu ilginç bulunarak sunuldu. Diskoid meniskusun tanı ve tedavi sorunları literatür bilgisi ışığı altında tartışıldı.

Grant Nelson, Amol Trivedi, Lucas Haase et al.

Rotator cuff pathology is the most common cause of shoulder-related disability. With an aging population that becomes more active, the incidence of rotator cuff dysfunction is expected to increase. Numerous strategies have been developed to address the persistently high failure rates following rotator cuff repair. Among these are synthetic and biological patches, which can be used either to augment and reinforce a reparable tear or act as an interposition graft to bridge gaps in irreparable tears. This review examined the various augmentation techniques currently available and provided an in-depth analysis of the literature regarding the benefits and limitations of each. We found that these grafts offer mechanical support while incorporating biological materials that promote more natural enthesis healing without triggering an inflammatory response. Many studies have shown improved clinical and rotator cuff healing outcomes when compared to preoperative conditions. However, prospective randomized controlled trials are needed to identify the optimal graft source.

Marwa Balaha, Barbara De Filippis, Monica Rapino et al.

<b>Objectives</b>: Bone defects, resulting from many causes, represent a challenge in maxillofacial and orthopedic surgery. Regenerative medicine offers promising strategies by introducing exogenous materials to modify the tissue environment and modulate the body’s natural healing mechanisms. Dental pulp stem cells (DPSCs) are considered an effective source for tissue repair. Small molecules such as caffeic acid phenethyl ester (CAPE), although having promising effects in promoting bone regeneration, are characterized by low chemical stability, which impairs their clinical application. This study aimed to investigate the bone regenerative capability of four CAPE derivatives, recently synthesized in our laboratory and selected based on previous studies. <b>Methods</b>: DPSCs were induced to osteogenic differentiation in the presence of these compounds (0–5 μM), and cell viability, matrix deposition, alkaline phosphatase activity, and osteogenic marker gene expression were evaluated. In addition, bone biomaterials composed of a chitosan/agarose matrix reinforced with nanohydroxyapatite and enriched with these CAPE derivatives were fabricated and assessed for cytotoxicity and cell adhesion. <b>Results</b>: Two of the tested compounds effectively enhanced DPSC differentiation toward the osteogenic lineage. The fabricated bone biomaterials showed no cytotoxicity and supported cell adhesion. Furthermore, these compounds demonstrated stability under various conditions, confirming their suitability for incorporation into bone biomaterials. <b>Conclusions</b>: The tested CAPE derivatives exhibit promising osteoinductive properties and stability, offering a valid alternative to traditional therapeutic strategies in regenerative medicine.

Xingrui Peng, Xiandi Wang, Tianhang Xie et al.

Michael S. Barnum, MD, Bryan M. Grommersch, MD, Samuel Hovland, BS et al.

Background: Sequential soft tissue releases are utilized in direct anterior approach (DAA) total hip arthroplasty (THA) as incomplete femoral exposure may lead to complications. This study identifies patient-specific parameters associated with soft tissue releases required for femoral exposure. Methods: A retrospective review was conducted on 133 patients (150 hips) who underwent primary THA via DAA with a single surgeon. Preoperative radiographic measurements included ilium-ischial ratio (IIR), anterior superior iliac spine to tip of the greater trochanter (AGT), femoral neck-shaft angle (FNA), and articulotrochanteric distance (ATD). Operative reports were reviewed and a multinomial logistic regression model was conducted to identify associations of soft tissue releases. Results: Among patients, 12 (8%) had no release, 94 (62%) had conjoined release, 44 (29%) had conjoined and piriformis releases. Multivariate analysis revealed IIR (OR [odds ratio] 1.68, P = .008), right laterality (OR 7.41, P = .025), and body mass index (BMI) (OR 1.26, P = .041) were associated with conjoined release. BMI (OR 1.51, P = .001), right laterality (OR 7.63, P = .038), and IIR (OR 2.06, P = .001) were also associated with piriformis release. There were no statistically significant differences between AGT, FNA, or ATD between groups. Conclusions: Patients with increased ilium to ischial ratio, right laterality, and larger BMI were associated with greater number of soft tissue releases for adequate femoral exposure. Surgeons may consider these factors to anticipate femoral releases or challenging femoral exposure in direct anterior total hip arthroplasty.

Hao Luo, Lin‐Feng Li, Song Han et al.

Abstract Purpose This study aims to describe a novel minimally invasive technique for the treatment of acute tibial posterior cruciate ligament (PCL) avulsion fracture. Methods This retrospective study included seven patients who underwent ultrasound‐guided fixation for acute PCL tibial avulsion fractures by using an adjustable‐loop device between January 2021 and January 2023. Before the surgery, the maximum diameter, area and displacement distance of the fragments were measured using computed tomography examination. All patients were followed up for at least 12 months, and clinical outcomes were assessed on the basis of range of motion, the International Knee Documentation Committee Score and the Lysholm score. Results For the seven patients, the mean maximum diameter, area and displacement distance of preoperative avulsion fragments were 12.7 mm (range, 9.0–48.3), 128 mm2 (range, 63–256.2) and 5.9 mm (range, 3.8–7.2), respectively. These fractures were fixed using an adjustable‐loop suspensory device under ultrasound guidance. Based on x‐ray examination during the post‐operative follow‐up period, all patients had no fracture displacement and fracture unions were confirmed, with a mean union time of 10.28 ± 2.13 weeks (range, 8–14). Based on the knee function assessment at 12‐month post‐operative follow‐up visit, all patients demonstrated excellent clinical outcomes. Conclusions Ultrasound‐assisted internal fixation using an adjustable‐loop device demonstrated satisfactory clinical and radiographic results. This technique has the advantages of being minimally invasive, safe, stable, convenient to operate and thus could be considered as a feasible alternative for the treatment of acute tibial PCL avulsion fractures. Level of Evidence Level III.

Oliver Sogard MD, John McDonald BS, Michael Elder Waters MD et al.

Category: Ankle; Trauma Introduction/Purpose: Ankle instability associated with fractures have increased surgical complexity and worse outcomes. Both the deltoid ligament and the syndesmotic ligament complex play pivotal roles in maintaining ankle stability. Medial clear space (MCS) widening serves as an indicator for ankle instability. Trans-syndesmotic fixation following open reduction and internal fixation of distal fibula has been used commonly to restore stability in unstable ankle fractures with MCS widening. Alternatively, anatomic repair of the deltoid ligament offers another approach for addressing MCS widening. However, there is no consensus on the best method for stabilizing the ankle. This study aims to provide a comprehensive analysis of current literature to compare the outcomes of trans-syndesmotic fixation and anatomic deltoid ligament repair in the treatment of unstable ankle fractures with MCS widening. Methods: This comprehensive literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing databases such as PubMed, Embase, Web of Science, and the Cochrane Library. The search was conducted on October 15, 2023. The criteria for including articles in this study were: (1) Patients who had undergone surgical fixation for unstable ankle fractures with medial clear space (MCS) widening, (2) Studies comparing clinical outcomes between trans-syndesmotic fixation and anatomic deltoid ligament repair to address MCS widening, (3) Studies reporting on at least one of the following outcomes: malreduction rates, necessity for hardware removal, wound complications, reoperation rates, and functional outcomes, including AOFAS (American Orthopaedic Foot and Ankle Society) scores and VAS (Visual Analog Scale) pain scores. Exclusion criteria eliminated studies involving: (1) Patients with medial malleolar fractures, (2) Revision surgeries, (3) Non-English publications, and (4) Case reports, systematic reviews, comments, editorials, surveys, or cadaver studies. Results: In this meta-analysis, a total of five studies were included. Medial clear space widening was treated with trans-syndesmotic screw fixation in 165 unstable ankle fractures, while 115 ankles underwent anatomic repair of the deltoid ligament. Anatomic deltoid ligament repair was significantly associated with a reduced risk of syndesmotic malreduction (Risk Ratio (RR)=0.26, 95% Confidence Interval (CI) = [0.10, 0.68]) and a lower likelihood of postoperative hardware removal (RR=0.06, 95% CI = [0.02, 0.14]). No significant differences were found in minor or major wound complications, reoperation rate, AOFAS and VAS scores. These findings highlight the advantages of anatomic deltoid ligament repair, which provides a more precise reduction of unstable ankle injuries with MCS widening and a reduced need for postoperative hardware removal, compared to trans-syndesmotic fixation. Conclusion: This study evaluated postoperative outcomes between trans-syndesmotic fixation and anatomic deltoid ligament repair in addressing MCS widening. Our analysis revealed that anatomic deltoid ligament repair resulted in a significantly lower rate of malreduction and a decreased necessity for postoperative hardware removal compared to trans-syndesmotic screw fixation. Both techniques showed similar rates of wound complications, reoperation, and equivalent functional and pain scores. These results call into question the trans-syndesmotic fixation alone for unstable ankle fractures with MCS widening. Anatomic repair of the deltoid ligament should be considered as a viable option to restore stability in unstable ankle fractures with MCS widening.

Magdalena Koszewicz, Dorota Kaminska, Jacek Martynkiewicz et al.

Peripheral neurological complications are seen after SARS-CoV-2 infections. These are mostly immune-mediated such as Guillaine–Barré syndrome or chronic inflammatory demyelinating polyneuropathy. We present a 39-year-old man treated with a right sciatic nerve allotransplantation with subsequent clinical and electrophysiological improvement within 30 months of observation. After SARS-CoV-2 infection, he developed clinical deterioration with selective sciatic nerve demyelination in a nerve conduction study. Nerve conduction velocity returned to previous values within six months of treatment. Intravenous immunoglobulins were used at standard dosage. The inflammatory immune process seemed to be a cause of peripheral demyelination isolated to a nerve allograft with good reaction for intravenous immunoglobulin treatment.

Lavan Rajan BA, Stephanie Eble AB, Jaeyoung Kim MD et al.

Background: Ankle fractures involving the posterior malleolus (PM) tend to result in inferior clinical outcomes compared to other ankle fractures. However, it is unclear which specific risk factors and fracture characteristics are associated with negative outcomes in these fractures. The aim of this study was to identify risk factors for poor postoperative patient-reported outcomes in patients with fractures involving the PM. Methods: This retrospective cohort study included patients who sustained ankle fractures involving the PM between March 2016 and July 2020 and had preoperative computed tomography (CT) scans. In total, 122 patients were included for analysis. One patient (0.8%) had an isolated PM fracture, 19 (15.6%) had bimalleolar ankle fractures involving the PM, and 102 (83.6%) had trimalleolar fractures. Fracture characteristics including the Lauge-Hansen (LH) and Haraguchi classifications and posterior malleolar fragment size were collected from preoperative CT scans. Patient Reported Outcome Measurement Information System (PROMIS) scores were collected preoperatively and at a minimum of 1 year postoperatively. The association between various demographic and fracture characteristics with postoperative PROMIS scores was assessed. Results: Involvement of more malleoli was associated with worse PROMIS Physical Function ( P  = .04), Global Physical Health ( P  = .04), and Global Mental Health ( P  < .001), and Depression scores ( P  = .001). Elevated BMI was also associated with worse PROMIS Physical Function ( P  = .0025), Pain Interference ( P  = .0013), and Global Physical Health ( P  = .012) scores. Time to surgery, fragment size, Haraguchi classification, and LH classification were not associated with PROMIS scores. Conclusion: In this cohort, we found that trimalleolar ankle fractures were associated with inferior PROMIS outcomes compared with bimalleolar ankle fractures involving the PM in multiple domains. Level of Evidence: Level III, retrospective cohort study.

Quen Oak Tang, Sherif Elnikety

Symptomatic Os acromiale can cause pain, impingement, and reduced range of movement. Disruption of the syndesmosis can result in significant pain and functional impairment; this may occur after trauma. Symptomatic Os acromiale is treated by either excision or fixation. Fixation via open technique is the mainstay of surgical intervention; however, recently, arthroscopic methods were used. In this technical note, we discuss the modification for all arthroscopic Os acromiale fixation; the fixation screws are introduced in anteroposterior fashion, employing the advances in orthopaedic fixation devices. Arthroscopic fixation is not widely adopted, possibly due to availability of implants and perceived difficult learning curve. We report this technique and demonstrate reproducibility with excellent results.

Mingtao Zhang, Zhitao Yang, Borong Zhang et al.

Abstract Background Rotator cuff tears are one of the most common shoulder injuries in the older population. This study aimed to determine whether acromioplasty reliably decreases the critical shoulder angle (CSA) and describe any associated complications. Methods A systematic literature review was performed according to PRISMA guidelines using PubMed, EMBASE, Web of Science, and Cochrane Library Database. Two reviewers independently screened the titles and abstracts using prespecified criteria. Studies where the acromioplasty was performed as a surgical procedure were included. Patient characteristics and degree of CSA reduction were collected from each individual study. All statistical analyses were performed using Review Manager (RevMan) 5.4.1 software. A random-effects model was used for meta-analysis. Results A total of 9 studies involving 1236 patients were included in the meta-analysis. The age of patients ranged from 23 to 82 years. The follow-up period ranged from 12 to 30 months. Of the 9 studies, 8 (88.9%) were retrospective, 1 (11.1%) was prospective, 5 were comparative, and 4 were case series. The mean CSA was significantly reduced from 36.1° ± 4.6° to 33.7° ± 4.2 (p < 0.05). The meta-analysis showed an overall best estimate of the mean difference in pre- and postoperative CSA equal to 2.63° (95% confidence interval: 2.15, 3.11] (p < 0.00001). Conclusions Acromioplasty can significantly reduce CSA, notably in cases of high preoperative CSA. In addition, the effect of lateral acromioplasty on the CSA was more significant compared to anterolateral acromioplasty. Acromioplasty was not associated with complications during the short-term follow-up.

John V. Horberg, MD, J. Ross Bailey, MD, Kathleen Kay, MD et al.

Background: There is no consensus on how to best address acetabular insufficiency. Several described techniques have a high rate of loosening and most rely on fixation to intact innominate bones. They also require extensive exposure and expensive implants. We present a novel technique for acetabular insufficiency management including discontinuity and a series with mean 6.5-year follow-up. Material and Methods: After exposure, a femoral neck osteotomy is made, or the femoral component is removed. Bone graft is reverse reamed into the defect, and a porous coated acetabular shell is implanted with screws for supplemental fixation. In 3-6 months, after defect healing, the femoral component is implanted. All staged total hip arthroplasties for pelvic discontinuity from 2010 to 2015 by a single provider with minimum 5-year follow-up were identified. Implant survivorship, Merle d’Aubinge, and visual analog scale scores as well as complications were recorded. Results: Nine patients were identified with mean 80.8-month follow-up (62-129). Merle D’Aubinge scores improved from 5.6 (4-8) to 15.3 (14-18), and Visual analog scale scores improved from 7.2 (6-9) to 0.8 (0-2). All implants were retained, and all patients were ambulatory at the terminal follow-up. There were 2 greater trochanter fractures, one calcar fracture managed with cerclage, and one patient developed heterotopic ossification. Conclusion: Staged total hip arthroplasty can be used to address pelvic discontinuity with excellent short- to mid-term outcomes. This technique allows for a more limited exposure and the use of primary hip implants. Fixation is by ingrowth and does not rely on intact pelvic architecture.

Ellen G. J. Ripmeester, Marjolein M. J. Caron, Guus G. H. van den Akker et al.

Abstract The fibrocartilage chondrocyte phenotype has been recognized to attribute to osteoarthritis (OA) development. These chondrocytes express genes related to unfavorable OA outcomes, emphasizing its importance in OA pathology. BMP7 is being explored as a potential disease-modifying molecule and attenuates the chondrocyte hypertrophic phenotype. On the other hand, BMP7 has been demonstrated to relieve organ fibrosis by counteracting the pro-fibrotic TGFβ-Smad3-PAI1 axis and increasing MMP2-mediated Collagen type I turnover. Whether BMP7 has anti-fibrotic properties in chondrocytes is unknown. Human OA articular chondrocytes (HACs) were isolated from end-stage OA femoral cartilage (total knee arthroplasty; n = 18 individual donors). SW1353 cells and OA HACs were exposed to 1 nM BMP7 for 24 h, after which gene expression of fibrosis-related genes and fibrosis-mediating factors was determined by RT-qPCR. In SW1353, Collagen type I protein levels were determined by immunocytochemistry and western blotting. PAI1 and MMP2 protein levels and activity were measured with an ELISA and activity assays, respectively. MMP2 activity was inhibited with the selective MMP-2 inhibitor OA-Hy. SMAD3 activity was determined by a (CAGA)12-reporter assay, and pSMAD2 levels by western blotting. Following BMP7 exposure, the expression of fibrosis-related genes was reduced in SW1353 cells and OA HACs. BMP7 reduced Collagen type I protein levels in SW1353 cells. Gene expression of MMP2 was increased in SW1353 cells following BMP7 treatment. BMP7 reduced PAI1 protein levels and -activity, while MMP2 protein levels and -activity were increased by BMP7. BMP7-dependent inhibition of Collagen type I protein levels in SW1353 cells was abrogated when MMP2 activity was inhibited. Finally, BMP7 reduced pSMAD2 levels determined by western blotting and reduced SMAD3 transcriptional activity as demonstrated by decreased (CAGA)12 luciferase reporter activity. Our data demonstrate that short-term exposure to BMP7 decreases the fibrocartilage chondrocyte phenotype. The BMP7-dependent reduction of Collagen type I protein expression seems MMP2-dependent and inhibition of Smad2/3-PAI1 activity was identified as a potential pathway via which BMP7 exerts its anti-fibrotic action. This indicates that in chondrocytes BMP7 may have a double mode-of-action by targeting both the hypertrophic as well as the fibrotic chondrocyte phenotype, potentially adding to the clinical relevance of using BMP7 as an OA disease-modifying molecule.

B. Bal, M. Rahaman