Total knee arthroplasty following surgical treatment of tibial plateau fractures - A retrospective cohort study.

BACKGROUND: Previous studies have shown the risk of post-traumatic osteoarthritis to be high following tibial plateau fracture surgery. Several investigations have examined the risk of total knee arthroplasty (TKA) following tibial plateau fracture treatment, but the risk of TKA in relation to the general population in Sweden has not previously been explored. AIM: To determine the incidence of TKA following surgical treatment of tibial plateau fractures and compare it with that of an age-matched population in Sweden. METHODS: A total of 349 tibial plateau fractures treated with open reduction internal fixation between 2002 and 2010 were identified from local hospital registers using diagnosis and surgical codes. The cohort was cross-matched with the Swedish Knee Arthroplasty Register to determine which patients had been treated with TKA within 10 years of fracture surgery. The incidence of primary TKA in the age-matched population in Sweden was obtained from the National Patient Register for comparison. RESULTS: Mortality-adjusted prevalence of TKA at 10 years following fracture surgery was 6.7% (relative risk (RR) = 5.5) and peaked during the second postoperative year (RR=19.3). High age was independently associated with increased risk of TKA (P=0.004); no other examined patient factors were significantly associated with TKA. CONCLUSION: The overall prevalence of TKA at 10 years following tibial plateau fracture surgery is low at 6.7%, however the risk is many times greater than that of the age-matched population in Sweden. The majority of patients require TKA within a few years of fracture treatment, hence post-traumatic osteoarthritis may arguably have not been the reason for TKA as this would have taken longer to develop.

Association of serum biomarkers with radiographic knee osteoarthritis, knee pain and function in a young, male, trauma-exposed population - Findings from the ADVANCE study.

OBJECTIVE: The ArmeD SerVices TrAuma RehabilitatioN OutComE (ADVANCE) study is investigating long-term combat-injury outcomes; this sub-study aims to understand the association of osteoarthritis (OA) biomarkers with knee radiographic OA (rOA), pain and function in this high-risk population for post-traumatic OA. DESIGN: ADVANCE compares combat-injured participants with age, rank, deployment and job-role frequency-matched uninjured participants. Post-injury immunoassay-measured serum biomarkers, knee radiographs, Knee Injury and Osteoarthritis Outcome Scale, and six-minute walk tests are reported. The primary analysis, adjusted for age, body mass, socioeconomic status, and ethnicity, was to determine any differences in biomarkers between those with/without combat injury, rOA and pain. Secondary analyses were performed to compare post-traumatic/idiopathic OA, painful/painfree rOA and injury patterns. RESULTS: A total of 1145 male participants were recruited, aged 34.1 ± 5.4, 8.9 ± 2.2 years post-injury (n = 579 trauma-exposed, of which, traumatic-amputation n = 161) or deployment (n = 566 matched). Cartilage oligomeric matrix protein (COMP) was significantly higher in the combat-injured group compared to uninjured (p = 0.01). Notably, COMP was significantly lower in the traumatic-amputation group compared to non-amputees (p < 0.001), decreasing relative to number of amputations (p < 0.001). Leptin was higher (p = 0.005) and adiponectin lower (p = 0.017) in those with v without knee pain, associated with an increased risk of 22% and 17% for pain, and 46% and 34% for painful rOA, respectively. There were no significant differences between trauma-exposed and unexposed participants with rOA. CONCLUSIONS: The most notable findings of this large, unique study are the similarities between those with rOA regardless of trauma-exposure, the injury-pattern and traumatic-amputation-associated differences in COMP, and the relationship between adipokines and pain.

Structure and Function Are Not the Same: The Case for Restoring Mechanoreceptor Continuity Following Anterior Cruciate Ligament Injury.

Anterior cruciate ligament (ACL) injury, particularly in increasingly young and active adolescents, continues to pose a clinical challenge with re-injury rates reported as high as 30%. Evidence also suggests that current standard-of-care ACL reconstruction (ACLR) does not mitigate post-traumatic osteoarthritis (PTOA) risk. Bridge- enhanced ACL restoration (BEAR) is a recently developed and tested ACL surgery that promotes primary healing of the native ACL with excellent early results. BEAR has shown to reduce signs of early PTOA compared to ACLR in an animal model. Here, we describe a theoretical framework related to re-innervation that can clarify why the outcomes of ACLR and BEAR surgeries differ. We also discuss how ongoing and new challenges in determining return-to-sport readiness following the competing surgeries may differ, and how emerging imaging tools and measures of neuromuscular function may aid in clinical decision-making to decrease the likelihood of re-injury and PTOA risk.

Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review.

The importance of mechanical loading and its relationship to orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA) is beginning to receive attention. This review explores the current efficacy of orthobiologic interventions, notably platelet-rich plasma (PRP), bone marrow aspirate (BMA), and mesenchymal stem/stromal cells (MSCs), in combating PTOA drawing from a comprehensive review of both preclinical animal models and human clinical studies. This review suggests why mechanical joint loading, such as running, might improve outcomes in PTOA management in conjunction with orthiobiologic administration. Accumulating evidence underscores the influence of mechanical loading on chondrocyte behavior and its pivotal role in PTOA pathogenesis. Dynamic loading has been identified as a key factor for optimal articular cartilage (AC) health and function, offering the potential to slow down or even reverse PTOA progression. We hypothesize that integrating the activation of mechanotransduction pathways with orthobiologic treatment strategies may hold a key to mitigating or even preventing PTOA development. Specific loading patterns incorporating exercise and physical activity for optimal joint health remain to be defined, particularly in the clinical setting following joint trauma.

Anterior cruciate ligament injury and age affect knee cartilage T2 but not thickness.

OBJECTIVE: To investigate the effect of unilateral anterior cruciate ligament (ACL) injury on cartilage thickness and composition, specifically laminar transverse relaxation time (T2) by magnetic resonance imaging (MRI), in younger and older participants and to compare within-person side differences in these parameters between ACL-injured and healthy controls. DESIGN: Quantitative double-echo steady-state 3 Tesla MRI-sequences were acquired in both knees of 85 participants in four groups: 20-30 years: healthy, HEA20-30, n = 24; ACL-injured, ACL20-30, n = 23; 40-60 years: healthy, HEA40-60, n = 24; ACL-injured, ACL40-60, n = 14 (ACL injury 2-10 years prior to study inclusion). Weight-bearing femorotibial cartilages were manually segmented; cartilage T2 and thickness were computed using custom software. Mean and side differences in subregional cartilage thickness, superficial and deep cartilage T2 were compared within and between groups using non-parametric statistics. RESULTS: Cartilage thickness did not differ within or between groups. Only the side difference in medial femorotibial cartilage thickness was greater in ACL20-30 than in HEA20-30. Deep zone T2 was longer in the ACL-injured than in the contralateral uninjured knees and than in healthy controls, especially in the lateral compartment. Most ACL-injured participants had side differences in femorotibial deep zone T2 above the threshold derived from controls. CONCLUSION: In the ACL-injured knee, early compositional differences in femorotibial cartilage (T2) appear to occur in the deep zone and precede cartilage thickness loss. These results suggest that monitoring laminar T2 after ACL injury may be useful in diagnosing and monitoring early articular cartilage changes.

Early microRNA and metabolite changes after anterior cruciate ligament reconstruction surgery.

OBJECTIVES: Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA's natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males. METHODS: A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2 weeks, and 6 weeks post-surgery (129 biospecimens in total). High-throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre-surgery versus 2 and 6 weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed. RESULTS: Levels of 46 miRNAs were increased at 2 weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2 weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2 weeks (log2-fold-change 0.71, 95%CI 0.22,1.20) and 6 weeks (log2-fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2 weeks (log2-fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6 weeks (log2-fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2 weeks post-surgery in females compared to males: L-leucine (-1.44, 95%CI -1.75,-1.13), g-guanidinobutyrate (-1.27, 95%CI 1.54,-0.99), creatinine (-1.17, 95%CI -1.44,-0.90), 2-methylbutyrylcarnitine (-1.76, 95%CI -2.17,-1.35), and leu-pro (-1.13, 95%CI -1.44,-0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males. CONCLUSION: MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA.

Potential Roles of Inflammation on Post-Traumatic Osteoarthritis of the Ankle.

Post-traumatic osteoarthritis of the ankle (PTOA) is frequently observed following a debilitating consequence of intra-articular ankle fractures. Numerous risk factors contribute to the pathogenesis of PTOA, including articular incongruity, joint malalignment, and concomitant soft tissue damage. Despite attempts to restore joint anatomy and manage soft tissues to avoid long-term complications after intra-articular ankle fractures, the incidence of PTOA remains markedly elevated. Inflammatory processes triggered by intra-articular ankle fractures have emerged as potential instigators that expedite the progression of PTOA. Injury to the articular cartilage and subchondral bone may lead to the release of inflammatory mediators, which can contribute to cartilage degradation and bone resorption. This study provides a narrative review on the current knowledge concerning the association between inflammation and the development of PTOA following intra-articular ankle fractures. We also discuss novel therapeutic agents that target inflammatory pathways to impede the progression of post-traumatic osteoarthritis after intra-articular ankle fractures. These medication and interventions were summarized within this review article.

Exercise following joint distraction inhibits muscle wasting and delays the progression of post-traumatic osteoarthritis in rabbits by activating PGC-1α in skeletal muscle.

OBJECTIVE: Muscle wasting frequently occurs following joint trauma. Previous research has demonstrated that joint distraction in combination with treadmill exercise (TRE) can mitigate intra-articular inflammation and cartilage damage, consequently delaying the advancement of post-traumatic osteoarthritis (PTOA). However, the precise mechanism underlying this phenomenon remains unclear. Hence, the purpose of this study was to examine whether the mechanism by which TRE following joint distraction delays the progression of PTOA involves the activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), as well as its impact on muscle wasting. METHODS: Quadriceps samples were collected from patients with osteoarthritis (OA) and normal patients with distal femoral fractures, and the expression of PGC-1α was measured. The hinged external fixator was implanted in the rabbit PTOA model. One week after surgery, a PGC-1α agonist or inhibitor was administered for 4 weeks prior to TRE. Western blot analysis was performed to detect the expression of PGC-1α and Muscle atrophy gene 1 (Atrogin-1). We employed the enzyme-linked immunosorbent assay (ELISA) technique to examine pro-inflammatory factors. Additionally, we utilized quantitative real-time polymerase chain reaction (qRT-PCR) to analyze genes associated with cartilage regeneration. Synovial inflammation and cartilage damage were evaluated through hematoxylin-eosin staining. Furthermore, we employed Masson's trichrome staining and Alcian blue staining to analyze cartilage damage. RESULTS: The decreased expression of PGC-1α in skeletal muscle in patients with OA is correlated with the severity of OA. In the rabbit PTOA model, TRE following joint distraction inhibited the expressions of muscle wasting genes, including Atrogin-1 and muscle ring finger 1 (MuRF1), as well as inflammatory factors such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in skeletal muscle, potentially through the activation of PGC-1α. Concurrently, the production of IL-1ß, IL-6, TNF-α, nitric oxide (NO), and malondialdehyde (MDA) in the synovial fluid was down-regulated, while the expression of type II collagen (Col2a1), Aggrecan (AGN), SRY-box 9 (SOX9) in the cartilage, and superoxide dismutase (SOD) in the synovial fluid was up-regulated. Additionally, histological staining results demonstrated that TRE after joint distraction reduced cartilage degeneration, leading to a significant decrease in OARSI scores.TRE following joint distraction could activate PGC-1α, inhibit Atrogin-1 expression in skeletal muscle, and reduce C-telopeptides of type II collagen (CTX-II) in the blood compared to joint distraction alone. CONCLUSION: Following joint distraction, TRE might promote the activation of PGC-1α in skeletal muscle during PTOA progression to exert anti-inflammatory effects in skeletal muscle and joint cavity, thereby inhibiting muscle wasting and promoting cartilage regeneration, making it a potential therapeutic intervention for treating PTOA.

Assessment of post-trauma microstructural alterations in the rabbit knee cartilage and subchondral bone.

Early diagnosis of post-traumatic osteoarthritis (PTOA) is critical for designing better treatments before the degradation becomes irreversible. We utilized multimodal high-resolution imaging to investigate early-stage deterioration in articular cartilage and the subchondral bone plate from a sub-critical impact to the knee joint, which initiates PTOA. The knee joints of 12 adult rabbits were mechanically impacted once on the femoral articular surface to initiate deterioration. At 2- and 14-week post-impact surgery, cartilage-bone blocks were harvested from the impact region in the animals (N = 6 each). These blocks were assessed for deterioration using polarized light microscopy (PLM), microcomputed tomography (µCT), and biochemical analysis. Statistically significant changes were noted in the impact tissues across the calcified zone (CZ) at 14 weeks post-impact: the optical retardation values in the CZ of impact cartilage had a drop of 29.0% at 14 weeks, while the calcium concentration in the CZ of impact cartilage also had a significant drop at 14 weeks. A significant reduction of 6.3% in bone mineral density (BMD) was noted in the subchondral bone plate of the impact samples at 14 weeks. At 2 weeks post-impact, only minor, non-significant changes were measured. Furthermore, the impact knees after 14 weeks had greater structural changes compared with the 2-week impact knees, indicating progressive degradation over time. The findings of this study facilitated a connection between mineralization alterations and the early deterioration of knee cartilage after a mechanical injury. In a broader context, these findings can be beneficial in improving clinical strategies to manage joint injuries.

Patient-Reported Outcomes following Tibial Plateau Fractures: Mid- to Short-Term Implications for Knee Function and Activity Level.

Background: Patients with complex proximal tibial plateau fractures (TPFs) tend to overestimate the prognosis of their injury, potentially due to factors such as a limited understanding, optimism, and the influence of the pain intensity. Understanding the reasons behind this misperception is crucial for healthcare providers to effectively communicate with patients and establish realistic expectations for treatment outcomes. The purpose of this study was to analyze the outcomes of TPFs, with a particular focus on patient-reported outcome measures concerning functional recovery, pain levels, and overall satisfaction with treatment. The authors aim to provide valuable insights into the realistic expectations and potential limitations that patients may encounter during their recovery journey. Methods: In this retrospective single-center study, all surgically treated TPFs between January 2014 and December 2019 with a minimum follow-up of 12 months were included. Several patient-reported outcome measures were obtained, including the International Knee documentation Committee Score (IKDC), Lyholm score, Tegner score, and visual analog scale (VAS) for pain. Fractures were classified according to Schatzker, and then subgrouped into simple (Schatzker I-III) and complex (Schatzker IV-VI) fractures. Results: A total of 54 patients (mean age 51.1 ± 11.9 years, 59.3% female) with a mean follow-up time of 3.9 years were included. Schatzker II fractures were present in 48% (n = 26) of the cases, with Schatzker III in 6% (n = 3), Schatzker IV fractures in 6% (n = 3), and Schatker VI fractures in 41% (n = 22) of the cases. All outcome scores showed a significant improvement between the first year after surgery and the last follow-up (mean: 3.9 years). Simple fractures showed significantly lower patient-reported outcomes when compared to the preinjury state; however, good to excellent results were observed. Patient-reported outcomes of complex fractures showed no significant changes in the study period with good to excellent results. When it comes to the Lysholm score, there were no significant differences in the outcome between simple and complex fractures. Furthermore, there was a return-to-sports rate of 100%, with high rates of changing sporting activity in 25% (simple fractures) and 45% in complex fractures. Conclusions: The data from this study showed that both simple and complex tibial plateau fractures show favorable outcomes at the midterm follow-up, and that injury severity does not correlate with worse results. While patients may tend to overestimate the recovery speed, this research highlights the importance of long-term follow-up, demonstrating a substantial improvement between one year post-surgery and the final evaluation. Return-to-sports rates were high, with adjustments needed for certain activities. However, patients should recognize the need to shift to lower-impact sports and the lengthy recovery process.

Toward designing human intervention studies to prevent osteoarthritis after knee injury: A report from an interdisciplinary OARSI 2023 workshop.

Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.

Finding the Goldilocks Zone of Mechanical Loading: A Comprehensive Review of Mechanical Loading in the Prevention and Treatment of Knee Osteoarthritis.

In this review, we discuss the interaction of mechanical factors influencing knee osteoarthritis (KOA) and post-traumatic osteoarthritis (PTOA) pathogenesis. Emphasizing the importance of mechanotransduction within inflammatory responses, we discuss its capacity for being utilized and harnessed within the context of prevention and rehabilitation of osteoarthritis (OA). Additionally, we introduce a discussion on the Goldilocks zone, which describes the necessity of maintaining a balance of adequate, but not excessive mechanical loading to maintain proper knee joint health. Expanding beyond these, we synthesize findings from current literature that explore the biomechanical loading of various rehabilitation exercises, in hopes of aiding future recommendations for physicians managing KOA and PTOA and athletic training staff strategically planning athlete loads to mitigate the risk of joint injury. The integration of these concepts provides a multifactorial analysis of the contributing factors of KOA and PTOA, in order to spur further research and illuminate the potential of utilizing the body's own physiological responses to mechanical stimuli in the management of OA.

Assessment of articular cartilage degradation in response to an impact injury using µMRI.

PURPOSE: Degradation of articular cartilage (AC) due to injury to the knee joint may initiate post-traumatic osteoarthritis (PTOA). Failure to diagnose the onset of the disease at an early stage makes the cure ineffective for PTOA. This study investigated the consequences of a mechanical injury to the knee in a rabbit model using microscopic magnetic resonance imaging (µMRI) at high resolution. MATERIALS AND METHODS: A mechanical injury was induced to the knee joints of 12 rabbits. Cartilage blocks were extracted from the non-impacted and impacted knee joints after 2 and 14 weeks post-impact. The specimens were studied using µMRI T2 relaxation and inductively coupled plasma analysis to determine the early degradation of the articular cartilage. RESULTS: The data established a connection between T2 relaxation time and the early progression of knee PTOA after an impact injury. T2 values were found to be higher in the impacted cartilage at both 2 and 14 weeks, in particular, T2-55° values in the impacted samples displayed a significant rise of 6.93% after 2 weeks and 20.02% after 14 weeks. Lower glycosaminoglycan measurement and higher water content in the impacted cartilage confirmed the µMRI results. CONCLUSIONS: This µMRI T2 study was able to detect cartilage damage in the impacted knees. In addition, greater degradation in the affected knees at 14 weeks than at 2 weeks indicated the progressive nature of cartilage deterioration over time. The µMRI results were in accord with the biochemical analysis, indicating the detection of early structural damage in the cartilage.

Exercise-induced modulation of myokine irisin on muscle-bone unit in the rat model of post-traumatic osteoarthritis.

BACKGROUND AND AIM: Post-traumatic osteoarthritis (PTOA) is a subtype of osteoarthritis (OA). Exercise may produce and release the myokine irisin through muscle fiber contraction. However, the effect of exercise-promoted irisin production on the internal interactions of the muscle-bone unit in PTOA studies remains unclear. METHODS: Eighteen 8-week-old Sprague-Dawley (SD) rats were randomly divided into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). The PTOA model was established by transection of anterior cruciate ligament (ACLT) and destabilization of medial meniscus (DMM). After 4 weeks of modeling, the PTOA/TW group underwent treadmill exercise (15 m/min, 30 min/d, 5 d/ week, 8 weeks), and the other two groups were free to move in the cage. Evaluation and correlation analysis of muscle, cartilage, subchondral bone and serological indexes were performed after euthanasia. RESULTS: Eight weeks of treadmill exercise effectively alleviated the trauma-induced OA phenotype, thereby maintaining cartilage and subchondral bone integrity in PTOA, and reducing quadriceps atrophy and myofibril degradation. Exercise reversed the down-regulated expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and fibronectin type III structural domain protein 5 (FNDC5) in muscle tissue of PTOA rats, and increased the blood irisin level, and the irisin level was positively correlated with the expression of PGC-1α and FNDC5. In addition, correlation analysis showed that irisin metabolism level was strongly negatively correlated with Osteoarthritis Research Society International (OARSI) and subchondral bone loss, indicating that irisin may be involved in cartilage biology and PTOA-related changes in cartilage and subchondral bone. Moreover, the metabolic level of irisin was strongly negatively correlated with muscle fiber cross-sectional area (CSA), Atrogin-1 and muscle ring-finger protein-1(MuRF-1) expression, suggesting that irisin may alleviate muscle atrophy through autocrine action. CONCLUSION: Treadmill exercise can alleviate the atrophy and degeneration of muscle fibers in PTOA rats, reduce the degradation of muscle fibrin, promote the expression of serum irisin, and alleviate the degeneration of articular cartilage and subchondral bone loss in PTOA rats. These results indicate that treadmill exercise can affect the process of PTOA by promoting the expression of myokine irisin in rat muscle-bone unit.

The Actin Cytoskeleton as a Regulator of Proteoglycan 4.

OBJECTIVE: The superficial zone (SZ) of articular cartilage is responsible for distributing shear forces for optimal cartilage loading and contributes to joint lubrication through the production of proteoglycan 4 (PRG4). PRG4 plays a critical role in joint homeostasis and is chondroprotective. Normal PRG4 production is affected by inflammation and irregular mechanical loading in post-traumatic osteoarthritis (PTOA). THe SZ chondrocyte (SZC) phenotype, including PRG4 expression, is regulated by the actin cytoskeleton in vitro. There remains a limited understanding of the regulation of PRG4 by the actin cytoskeleton in native articular chondrocytes. The filamentous (F)-actin cytoskeleton is a potential node in crosstalk between mechanical stimulation and cytokine activation and the regulation of PRG4 in SZCs, therefore developing insights in the regulation of PRG4 by actin may identify molecular targets for novel PTOA therapies. MATERIALS AND METHODS: A comprehensive literature search on PRG4 and the regulation of the SZC phenotype by actin organization was performed. RESULTS: PRG4 is strongly regulated by the actin cytoskeleton in isolated SZCs in vitro. Biochemical and mechanical stimuli have been characterized to regulate PRG4 and may converge upon actin cytoskeleton signaling. CONCLUSION: Actin-based regulation of PRG4 in native SZCs is not fully understood and requires further elucidation. Understanding the regulation of PRG4 by actin in SZCs requires an in vivo context to further potential of leveraging actin arrangement to arthritic therapeutics.

Investigation Into the Effects of Intra-Articular Steroid on Post-Traumatic Osteoarthritis in Distal Radius Fractures: A Randomized Controlled Pilot Study.

PURPOSE: The aim of this prospective, randomized, controlled, double-blinded pilot study was to determine the rates of post-traumatic osteoarthritis and assess joint space width in the presence or absence of a single intra-articular injection of corticosteroid after an acute, intra-articular distal radius fracture (DRF). METHODS: Forty patients received a single, intra-articular, radiocarpal joint injection of 4 mg of dexamethasone (DEX) (n = 19) or normal saline placebo (n = 21) within 2 weeks of a surgically or nonsurgically treated intra-articular DRF. The primary outcome measure was minimum radiocarpal joint space width (mJSW) on noncontrast computed tomography scans at 2 years postinjection. Secondary outcomes were obtained at 3 months, 6 months, 1 year, and 2 years postinjection and included Disabilities of the Arm, Shoulder, and Hand; Michigan Hand Questionnaire; Patient-Rated Wrist Evaluation; wrist range of motion; and grip strength. RESULTS: At 2-year follow-up, there was no difference in mean mJSW between the DEX group (2.2 mm; standard deviation, 0.6; range, 1.4-3.2) and the placebo group (2.3 mm; standard deviation, 0.7; range, 0.9-3.9). Further, there were no differences in any secondary outcome measures at any postinjection follow-up interval. CONCLUSIONS: Radiocarpal joint injection of corticosteroid within 2 weeks of an intra-articular DRF does not appear to affect the development of post-traumatic osteoarthritis within 2 years follow-up in a small pilot cohort. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Comparisons of ankle arthrodesis with different internal fixation methods in the treatment of post-traumatic osteoarthritis.

BACKGROUND: The aim of this study was to explore the clinical efficacy of ankle arthrodesis with different internal fixation methods in the treatment of post-traumatic osteoarthritis. METHODS: We collected 85 patients with post-traumatic osteoarthritis who underwent different ankle arthrodesis between December 2015 and December 2020. The operation performance, complication rate, hindfoot alignment, talus tilt angle, visual analogue scale (VAS), and American Orthopedic Foot and Ankle Society (AOFAS) score were preoperatively and postoperatively evaluated. RESULTS: In an anterior approach, the locking plate-fixation exhibited a similarity in operation time, incision length, postoperative drainage, bone fusion, hindfoot alignment, and talus tilt angle with fibula support compression screw-fixation, but it was better in increasing postoperative AOFAS. The locking plate-fixation in the anterior approach had lower operation time, incision length, and postoperative drainage than that in the lateral approach. In addition, the lateral locking plate combined with posterolateral compression screw fixation (LLPPCSF) presented shorter bone fusion time, higher AOFAS score, and lower complication rate than either plate- or screw-fixation alone. CONCLUSION: Lateral locking plate fixation was better than fibula support compression screw fixation in relieving postoperative pain. Anterior locking plate fixation was more time-saving and less invasiveness than lateral locking plate fixation, but its application was limited in low degree of ankle deformation. LLPPCSF was the most effective in improving bone fusion and postoperative pain, considering an optimal option for the treatment of post-traumatic osteoarthritis.

The Risk Factors and Preventive Strategies of Poor Knee Functions and Osteoarthritis after Anterior Cruciate Ligament Reconstruction: A Narrative Review.

Anterior cruciate ligament reconstruction (ACLR) is the standard surgical treatment for ACL injury, which typically uses a graft to replace the torn ligament in the knee that uses small incisions with minimally invasive surgery. The optimal knee functions following ACLR depend on rehabilitation processes before and after the surgery. Knee function is the ability of the knee to perform various types of functional movements like walking, squatting, running, jumping, and pivoting where patients expect to achieve maximum knee function or at least more than 80% of its initial condition before the injury to avoid being categorized as poor knee function after ACLR. Patients use patient-reported outcome measures to collect data on their health status and quality of life after ACLR. Post-traumatic osteoarthritis (PTOA) is a type of OA that manifests in local cartilage injury caused by chondrocyte death, and matrix dispersion occurs following a joint injury like ACL injury. Gender, time from injury to surgery, and graft type were considered as risk factors for poor knee function after ACLR, while overweight, meniscus tear, and cartilage defect as risk factors for PTOA. However, age is an internal risk factor for both poor knee function and PTOA following ACLR. This review suggests several strategies to prevent both conditions, including a pre-operative program, comprehensive rehabilitation, body weight control, and return to sport (RTS) consideration based on physical capacity, proper time, and psychological readiness.

Imaging mass cytometry reveals tissue-specific cellular immune phenotypes in the mouse knee following ACL injury.

Objective: To develop an imaging mass cytometry method for identifying complex cell phenotypes, inter-cellular interactions, and population changes in the synovium and infrapatellar fat pad (IFP) of the mouse knee following a non-invasive compression injury. Design: Fifteen male C57BL/6 mice were fed a high-fat diet for 8 weeks prior to random assignment to sham, 0.88 â€‹mm, or 1.7 â€‹mm knee compression displacement at 24 weeks of age. 2-weeks after loading, limbs were prepared for histologic and imaging mass cytometry analysis, focusing on myeloid immune cell populations in the synovium and IFP. Results: 1.7 â€‹mm compression caused anterior cruciate ligament (ACL) rupture, development of post-traumatic osteoarthritis, and a 2- to 3-fold increase in cellularity of synovium and IFP tissues compared to sham or 0.88 â€‹mm compression. Imaging mass cytometry identified 11 myeloid cell subpopulations in synovium and 7 in IFP, of which approximately half were elevated 2 weeks after ACL injury in association with the vasculature. Notably, two monocyte/macrophage subpopulations and an MHC IIhi population were elevated 2-weeks post-injury in the synovium but not IFP. Vascular and immune cell interactions were particularly diverse in the synovium, incorporating 8 unique combinations of 5 myeloid cell populations, including a monocyte/macrophage population, an MHC IIhi population, and 3 different undefined F4/80+ myeloid populations. Conclusions: Developing an imaging mass cytometry method for the mouse enabled us to identify a diverse array of synovial and IFP vascular-associated myeloid cell subpopulations. These subpopulations were differentially elevated in synovial and IFP tissues 2-weeks post injury, providing new details on tissue-specific immune regulation.