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The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 50 - 55
1 Jan 2018
Kono K Tomita T Futai K Yamazaki T Tanaka S Yoshikawa H Sugamoto K

Aims. In Asia and the Middle-East, people often flex their knees deeply in order to perform activities of daily living. The purpose of this study was to investigate the 3D kinematics of normal knees during high-flexion activities. Our hypothesis was that the femorotibial rotation, varus-valgus angle, translations, and kinematic pathway of normal knees during high-flexion activities, varied according to activity. Materials and Methods. We investigated the in vivo kinematics of eight normal knees in four male volunteers (mean age 41.8 years; 37 to 53) using 2D and 3D registration technique, and modelled the knees with a computer aided design program. Each subject squatted, kneeled, and sat cross-legged. We evaluated the femoral rotation and varus-valgus angle relative to the tibia and anteroposterior translation of the medial and lateral side, using the transepicodylar axis as our femoral reference relative to the perpendicular projection on to the tibial plateau. This method evaluates the femur medially from what has elsewhere been described as the extension facet centre, and differs from the method classically applied. . Results. During squatting and kneeling, the knees displayed femoral external rotation. When sitting cross-legged, femurs displayed internal rotation from 10° to 100°. From 100°, femoral external rotation was observed. No significant difference in varus-valgus angle was seen between squatting and kneeling, whereas a varus position was observed from 140° when sitting cross-legged. The measure kinematic pathway using our methodology found during squatting a medial pivoting pattern from 0° to 40° and bicondylar rollback from 40° to 150°. During kneeling, a medial pivot pattern was evident. When sitting cross-legged, a lateral pivot pattern was seen from 0° to 100°, and a medial pivot pattern beyond 100°. Conclusion. The kinematics of normal knees during high flexion are variable according to activity. Nevertheless, our study was limited to a small number of male patients using a different technique to report the kinematics than previous publications. Accordingly, caution should be observed in generalizing our findings. Cite this article: Bone Joint J 2018;100-B:50–5


Aims. Mobile-bearing unicompartmental knee arthroplasty (UKA) with a flat tibial plateau has not performed well in the lateral compartment, leading to a high rate of dislocation. For this reason, the Domed Lateral UKA with a biconcave bearing was developed. However, medial and lateral tibial plateaus have asymmetric anatomical geometries, with a slightly dished medial and a convex lateral plateau. Therefore, the aim of this study was to evaluate the extent at which the normal knee kinematics were restored with different tibial insert designs using computational simulation. Methods. We developed three different tibial inserts having flat, conforming, and anatomy-mimetic superior surfaces, whereas the inferior surface in all was designed to be concave to prevent dislocation. Kinematics from four male subjects and one female subject were compared under deep knee bend activity. Results. The conforming design showed significantly different kinematics in femoral rollback and internal rotation compared to that of the intact knee. The flat design showed significantly different kinematics in femoral rotation during high flexion. The anatomy-mimetic design preserved normal knee kinematics in femoral rollback and internal rotation. Conclusion. The anatomy-mimetic design in lateral mobile UKA demonstrated restoration of normal knee kinematics. Such design may allow achievement of the long sought normal knee characteristics post-lateral mobile UKA. However, further in vivo and clinical studies are required to determine whether this design can truly achieve a more normal feeling of the knee and improved patient satisfaction. Cite this article: Bone Joint Res 2020;9(7):421–428


Objectives. Preservation of both anterior and posterior cruciate ligaments in total knee arthroplasty (TKA) can lead to near-normal post-operative joint mechanics and improved knee function. We hypothesised that a patient-specific bicruciate-retaining prosthesis preserves near-normal kinematics better than standard off-the-shelf posterior cruciate-retaining and bicruciate-retaining prostheses in TKA. Methods. We developed the validated models to evaluate the post-operative kinematics in patient-specific bicruciate-retaining, standard off-the-shelf bicruciate-retaining and posterior cruciate-retaining TKA under gait and deep knee bend loading conditions using numerical simulation. Results. Tibial posterior translation and internal rotation in patient-specific bicruciate-retaining prostheses preserved near-normal kinematics better than other standard off-the-shelf prostheses under gait loading conditions. Differences from normal kinematics were minimised for femoral rollback and internal-external rotation in patient-specific bicruciate-retaining, followed by standard off-the-shelf bicruciate-retaining and posterior cruciate-retaining TKA under deep knee bend loading conditions. Moreover, the standard off-the-shelf posterior cruciate-retaining TKA in this study showed the most abnormal performance in kinematics under gait and deep knee bend loading conditions, whereas patient-specific bicruciate-retaining TKA led to near-normal kinematics. Conclusion. This study showed that restoration of the normal geometry of the knee joint in patient-specific bicruciate-retaining TKA and preservation of the anterior cruciate ligament can lead to improvement in kinematics compared with the standard off-the-shelf posterior cruciate-retaining and bicruciate-retaining TKA. Cite this article: Y-G. Koh, J. Son, S-K. Kwon, H-J. Kim, O-R. Kwon, K-T. Kang. Preservation of kinematics with posterior cruciate-, bicruciate- and patient-specific bicruciate-retaining prostheses in total knee arthroplasty by using computational simulation with normal knee model. Bone Joint Res 2017;6:557–565. DOI: 10.1302/2046-3758.69.BJR-2016-0250.R1


Bone & Joint Research
Vol. 8, Issue 12 | Pages 593 - 600
1 Dec 2019
Koh Y Lee J Lee H Kim H Chung H Kang K

Aims

Commonly performed unicompartmental knee arthroplasty (UKA) is not designed for the lateral compartment. Additionally, the anatomical medial and lateral tibial plateaus have asymmetrical geometries, with a slightly dished medial plateau and a convex lateral plateau. Therefore, this study aims to investigate the native knee kinematics with respect to the tibial insert design corresponding to the lateral femoral component.

Methods

Subject-specific finite element models were developed with tibiofemoral (TF) and patellofemoral joints for one female and four male subjects. Three different TF conformity designs were applied. Flat, convex, and conforming tibial insert designs were applied to the identical femoral component. A deep knee bend was considered as the loading condition, and the kinematic preservation in the native knee was investigated.


Bone & Joint Open
Vol. 1, Issue 7 | Pages 339 - 345
3 Jul 2020
MacDessi SJ Griffiths-Jones W Harris IA Bellemans J Chen DB

Aims. An algorithm to determine the constitutional alignment of the lower limb once arthritic deformity has occurred would be of value when undertaking kinematically aligned total knee arthroplasty (TKA). The purpose of this study was to determine if the arithmetic hip-knee-ankle angle (aHKA) algorithm could estimate the constitutional alignment of the lower limb following development of significant arthritis. Methods. A matched-pairs radiological study was undertaken comparing the aHKA of an osteoarthritic knee (aHKA-OA) with the mechanical HKA of the contralateral normal knee (mHKA-N). Patients with Grade 3 or 4 Kellgren-Lawrence tibiofemoral osteoarthritis in an arthritic knee undergoing TKA and Grade 0 or 1 osteoarthritis in the contralateral normal knee were included. The aHKA algorithm subtracts the lateral distal femoral angle (LDFA) from the medial proximal tibial angle (MPTA) measured on standing long leg radiographs. The primary outcome was the mean of the paired differences in the aHKA-OA and mHKA-N. Secondary outcomes included comparison of sex-based differences and capacity of the aHKA to determine the constitutional alignment based on degree of deformity. Results. A total of 51 radiographs met the inclusion criteria. There was no significant difference between aHKA-OA and mHKA-N, with a mean angular difference of −0.4° (95% SE −0.8° to 0.1°; p = 0.16). There was no significant sex-based difference when comparing aHKA-OA and mHKA-N (mean difference 0.8°; p = 0.11). Knees with deformities of more than 8° had a greater mean difference between aHKA-OA and mHKA-N (1.3°) than those with lesser deformities (-0.1°; p = 0.009). Conclusion. This study supports the arithmetic HKA algorithm for prediction of the constitutional alignment once arthritis has developed. The algorithm has similar accuracy between sexes and greater accuracy with lesser degrees of deformity. Cite this article: Bone Joint Open 2020;1-7:339–345


Bone & Joint Open
Vol. 2, Issue 5 | Pages 351 - 358
27 May 2021
Griffiths-Jones W Chen DB Harris IA Bellemans J MacDessi SJ

Aims. Once knee arthritis and deformity have occurred, it is currently not known how to determine a patient’s constitutional (pre-arthritic) limb alignment. The purpose of this study was to describe and validate the arithmetic hip-knee-ankle (aHKA) algorithm as a straightforward method for preoperative planning and intraoperative restoration of the constitutional limb alignment in total knee arthroplasty (TKA). Methods. A comparative cross-sectional, radiological study was undertaken of 500 normal knees and 500 arthritic knees undergoing TKA. By definition, the aHKA algorithm subtracts the lateral distal femoral angle (LDFA) from the medial proximal tibial angle (MPTA). The mechanical HKA (mHKA) of the normal group was compared to the mHKA of the arthritic group to examine the difference, specifically related to deformity in the latter. The mHKA and aHKA were then compared in the normal group to assess for differences related to joint line convergence. Lastly, the aHKA of both the normal and arthritic groups were compared to test the hypothesis that the aHKA can estimate the constitutional alignment of the limb by sharing a similar centrality and distribution with the normal population. Results. There was a significant difference in means and distributions of the mHKA of the normal group compared to the arthritic group (mean -1.33° (SD 2.34°) vs mean -2.88° (SD 7.39°) respectively; p < 0.001). However, there was no significant difference between normal and arthritic groups using the aHKA (mean -0.87° (SD 2.54°) vs mean -0.77° (SD 2.84°) respectively; p = 0.550). There was no significant difference in the MPTA and LDFA between the normal and arthritic groups. Conclusion. The arithmetic HKA effectively estimated the constitutional alignment of the lower limb after the onset of arthritis in this cross-sectional population-based analysis. This finding is of significant importance to surgeons aiming to restore the constitutional alignment of the lower limb during TKA. Cite this article: Bone Jt Open 2021;2(5):351–358


Aims. This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Methods. Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs. Results. We detected 1,212 DEmRNAs and 49 DElncRNAs in OA and normal knee cartilage. A total of 75 dysregulated lncRNA-miRNA interactions and 711 dysregulated miRNA-mRNA interactions were obtained in the ceRNA network, including ten DElncRNAs, 69 miRNAs, and 72 DEmRNAs. Similarly, 1,330 dysregulated lncRNA-mRNA interactions were used to construct the co-expression network, which included ten lncRNAs and 407 mRNAs. We finally identified seven hub lncRNAs, named MIR210HG, HCP5, LINC00313, LINC00654, LINC00839, TBC1D3P1-DHX40P1, and ISM1-AS1. Subsequent enrichment analysis elucidated that these lncRNAs regulated extracellular matrix organization and enriched in osteoclast differentiation, the FoxO signalling pathway, and the tumour necrosis factor (TNF) signalling pathway in the development of OA. Conclusion. The integrated analysis of the ceRNA network and co-expression network identified seven hub lncRNAs associated with OA. These lncRNAs may regulate extracellular matrix changes and chondrocyte homeostasis in OA progress. Cite this article:Bone Joint Res. 2020;9(3):90–98


Bone & Joint Open
Vol. 4, Issue 3 | Pages 210 - 218
28 Mar 2023
Searle HKC Rahman A Desai AP Mellon SJ Murray DW

Aims

To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics.

Methods

Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSWL) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%.


The Bone & Joint Journal
Vol. 105-B, Issue 12 | Pages 1271 - 1278
1 Dec 2023
Rehman Y Korsvold AM Lerdal A Aamodt A

Aims

This study compared patient-reported outcomes of three total knee arthroplasty (TKA) designs from one manufacturer: one cruciate-retaining (CR) design, and two cruciate-sacrificing designs, anterior-stabilized (AS) and posterior-stabilized (PS).

Methods

Patients scheduled for primary TKA were included in a single-centre, prospective, three-armed, blinded randomized trial (n = 216; 72 per group). After intraoperative confirmation of posterior cruciate ligament (PCL) integrity, patients were randomly allocated to receive a CR, AS, or PS design from the same TKA system. Insertion of an AS or PS design required PCL resection. The primary outcome was the mean score of all five subscales of the Knee injury and Osteoarthritis Outcome Score (KOOS) at two-year follow-up. Secondary outcomes included all KOOS subscales, Oxford Knee Score, EuroQol five-dimension health questionnaire, EuroQol visual analogue scale, range of motion (ROM), and willingness to undergo the operation again. Patient satisfaction was also assessed.


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1231 - 1239
1 Nov 2024
Tzanetis P Fluit R de Souza K Robertson S Koopman B Verdonschot N

Aims

The surgical target for optimal implant positioning in robotic-assisted total knee arthroplasty remains the subject of ongoing discussion. One of the proposed targets is to recreate the knee’s functional behaviour as per its pre-diseased state. The aim of this study was to optimize implant positioning, starting from mechanical alignment (MA), toward restoring the pre-diseased status, including ligament strain and kinematic patterns, in a patient population.

Methods

We used an active appearance model-based approach to segment the preoperative CT of 21 osteoarthritic patients, which identified the osteophyte-free surfaces and estimated cartilage from the segmented bones; these geometries were used to construct patient-specific musculoskeletal models of the pre-diseased knee. Subsequently, implantations were simulated using the MA method, and a previously developed optimization technique was employed to find the optimal implant position that minimized the root mean square deviation between pre-diseased and postoperative ligament strains and kinematics.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 20 - 27
1 Jan 2018
Kang K Son J Suh D Kwon SK Kwon O Koh Y

Objectives. Patient-specific (PS) implantation surgical technology has been introduced in recent years and a gradual increase in the associated number of surgical cases has been observed. PS technology uses a patient’s own geometry in designing a medical device to provide minimal bone resection with improvement in the prosthetic bone coverage. However, whether PS unicompartmental knee arthroplasty (UKA) provides a better biomechanical effect than standard off-the-shelf prostheses for UKA has not yet been determined, and still remains controversial in both biomechanical and clinical fields. Therefore, the aim of this study was to compare the biomechanical effect between PS and standard off-the-shelf prostheses for UKA. Methods. The contact stresses on the polyethylene (PE) insert, articular cartilage and lateral meniscus were evaluated in PS and standard off-the-shelf prostheses for UKA using a validated finite element model. Gait cycle loading was applied to evaluate the biomechanical effect in the PS and standard UKAs. Results. The contact stresses on the PE insert were similar for both the PS and standard UKAs. Compared with the standard UKA, the PS UKA did not show any biomechanical effect on the medial PE insert. However, the contact stresses on the articular cartilage and the meniscus in the lateral compartment following the PS UKA exhibited closer values to the healthy knee joint compared with the standard UKA. Conclusion. The PS UKA provided mechanics closer to those of the normal knee joint. The decreased contact stress on the opposite compartment may reduce the overall risk of progressive osteoarthritis. Cite this article: K-T. Kang, J. Son, D-S. Suh, S. K. Kwon, O-R. Kwon, Y-G. Koh. Patient-specific medial unicompartmental knee arthroplasty has a greater protective effect on articular cartilage in the lateral compartment: A Finite Element Analysis. Bone Joint Res 2018;7:20–27. DOI: 10.1302/2046-3758.71.BJR-2017-0115.R2


Aims

Classifying trochlear dysplasia (TD) is useful to determine the treatment options for patients suffering from patellofemoral instability (PFI). There is no consensus on which classification system is more reliable and reproducible for the purpose of guiding clinicians’ management of PFI. There are also concerns about the validity of the Dejour Classification (DJC), which is the most widely used classification for TD, having only a fair reliability score. The Oswestry-Bristol Classification (OBC) is a recently proposed system of classification of TD, and the authors report a fair-to-good interobserver agreement and good-to-excellent intraobserver agreement in the assessment of TD. The aim of this study was to compare the reliability and reproducibility of these two classifications.

Methods

In all, six assessors (four consultants and two registrars) independently evaluated 100 axial MRIs of the patellofemoral joint (PFJ) for TD and classified them according to OBC and DJC. These assessments were again repeated by all raters after four weeks. The inter- and intraobserver reliability scores were calculated using Cohen’s kappa and Cronbach’s α.


Bone & Joint Open
Vol. 4, Issue 12 | Pages 948 - 956
15 Dec 2023
Vella-Baldacchino M Webb J Selvarajah B Chatha S Davies A Cobb JP Liddle AD

Aims

With up to 40% of patients having patellofemoral joint osteoarthritis (PFJ OA), the two arthroplasty options are to replace solely the patellofemoral joint via patellofemoral arthroplasty (PFA), or the entire knee via total knee arthroplasty (TKA). The aim of this study was to assess postoperative success of second-generation PFAs compared to TKAs for patients treated for PFJ OA using patient-reported outcome measures (PROMs) and domains deemed important by patients following a patient and public involvement meeting.

Methods

MEDLINE, EMBASE via OVID, CINAHL, and EBSCO were searched from inception to January 2022. Any study addressing surgical treatment of primary patellofemoral joint OA using second generation PFA and TKA in patients aged above 18 years with follow-up data of 30 days were included. Studies relating to OA secondary to trauma were excluded. ROB-2 and ROBINS-I bias tools were used.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 536 - 545
8 Sep 2023
Luo P Yuan Q Yang M Wan X Xu P

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.


Bone & Joint Open
Vol. 5, Issue 8 | Pages 628 - 636
2 Aug 2024
Eachempati KK Parameswaran A Ponnala VK Sunil A Sheth NP

Aims

The aims of this study were: 1) to describe extended restricted kinematic alignment (E-rKA), a novel alignment strategy during robotic-assisted total knee arthroplasty (RA-TKA); 2) to compare residual medial compartment tightness following virtual surgical planning during RA-TKA using mechanical alignment (MA) and E-rKA, in the same set of osteoarthritic varus knees; 3) to assess the requirement of soft-tissue releases during RA-TKA using E-rKA; and 4) to compare the accuracy of surgical plan execution between knees managed with adjustments in component positioning alone, and those which require additional soft-tissue releases.

Methods

Patients who underwent RA-TKA between January and December 2022 for primary varus osteoarthritis were included. Safe boundaries for E-rKA were defined. Residual medial compartment tightness was compared following virtual surgical planning using E-rKA and MA, in the same set of knees. Soft-tissue releases were documented. Errors in postoperative alignment in relation to planned alignment were compared between patients who did (group A) and did not (group B) require soft-tissue releases.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Methods

Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.


The Bone & Joint Journal
Vol. 105-B, Issue 1 | Pages 35 - 46
1 Jan 2023
Mills K Wymenga AB Bénard MR Kaptein BL Defoort KC van Hellemondt GG Heesterbeek PJC

Aims

The aim of this study was to compare a bicruciate-retaining (BCR) total knee arthroplasty (TKA) with a posterior cruciate-retaining (CR) TKA design in terms of kinematics, measured using fluoroscopy and stability as micromotion using radiostereometric analysis (RSA).

Methods

A total of 40 patients with end-stage osteoarthritis were included in this randomized controlled trial. All patients performed a step-up and lunge task in front of a monoplane fluoroscope one year postoperatively. Femorotibial contact point (CP) locations were determined at every flexion angle and compared between the groups. RSA images were taken at baseline, six weeks, three, six, 12, and 24 months postoperatively. Clinical and functional outcomes were compared postoperatively for two years.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 33 - 45
16 Jan 2023
Li B Ding T Chen H Li C Chen B Xu X Huang P Hu F Guo L

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Methods

Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.


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.


Bone & Joint Research
Vol. 11, Issue 9 | Pages 652 - 668
7 Sep 2022
Lv G Wang B Li L Li Y Li X He H Kuang L

Aims

Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages.

Methods

Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot.