UNASSIGNED: Bucket-handle meniscal tears are large longitudinal vertical meniscal tears that have an attached fragment flipped into the intercondylar notch. Meniscal repair attempts to restore the function of the meniscus and aims to preserve joint mechanics. Alternatively, meniscectomy results in quicker recovery but may lead to future degeneration.
UNASSIGNED: To evaluate the long-term risk of subsequent ipsilateral knee surgery in patients who underwent a bucket-handle meniscal repair (BHMR) versus meniscectomy/bucket-handle meniscal debridement (BHMD) and assess risk factors associated with subsequent knee surgical intervention.
UNASSIGNED: Cohort study; Level of evidence, 3.
UNASSIGNED: An electronic health records search for all patients who underwent arthroscopic knee meniscal surgery (repair and meniscectomy) between 2011 and 2018 was performed. Natural language processing was used to search for terms of interest in the long operative notes to determine whether these surgeries were performed for bucket-handle meniscal tears. These patients comprised our initial cohort. Study patients were followed for at least 1 year and for up to 5 years (until December 31, 2019), with censoring at death or membership disenrollment. Baseline patient characteristics and outcomes were evaluated via a database review. The primary outcome was subsequent ipsilateral knee surgeries and secondary outcomes included contralateral knee surgeries, deep surgical site infections, and venous thrombotic events. Multivariable logistic regression analyses were used to model for subsequent surgical treatment of the ipsilateral knee. A subset analysis for patients aged 30 to 50 years was then performed.
UNASSIGNED: The median follow-up time was 52.4 months (interquartile range [IQR], 33.5-60 months). A total of 1359 patients underwent BHMR and 1537 patients underwent BHMD. The median age was 24 years (IQR, 17-34 years) for the BHMR versus 38 years (IQR, 27-47 years) for the BHMD group (P < .001). Body mass index (BMI) was significantly lower in the BHMR group compared with the BHMD group (P < .001). BHMR was significantly more likely to be performed during a concomitant ipsilateral anterior cruciate ligament reconstruction (ACLR) than a BHMD (44.2% vs 30.1%, P < .001). During the follow-up period, a total of 656 subsequent ipsilateral procedures were performed in 393 (13.6%) patients. Patients who underwent initial BHMR were at a significantly higher risk of undergoing subsequent meniscal repair (4.3% vs 1%, P < .001), meniscectomy (12.1% vs 3.3%, P < .001), and ACLR (7.4% vs 2.9%, P < .001) compared with those who underwent BHMD. Multivariable analysis showed that BHMR, younger age, and lower BMI were risk factors for subsequent ipsilateral surgery. After adjusting for patient demographic and clinical characteristics, subset analysis showed that for patients aged 30 to 50 years, undergoing a BHMR versus a BHMD led to a 2.3-fold higher risk of subsequent surgery, a 5.3-fold higher risk of subsequent meniscal repair and a 3.2-fold higher risk of subsequent meniscectomy.
UNASSIGNED: BHMR was more often performed in younger patients with a lower BMI, especially during a concomitant ACLR. Patients treated with BHMR were more likely to undergo subsequent surgeries, with the likelihood decreasing with increasing age. Subset analyses showed increasing risk for subsequent surgeries with BHMR versus BHMD in the cohort consisting of patients aged 30 to 50 years.

UNASSIGNED: Previous studies have demonstrated that medial meniscus posterior root tear (MMPRT) repair is superior to debridement in terms of patient-reported outcomes, rates of conversion to total knee arthroplasty (TKA), and long-term costs. Despite the known poor midterm outcomes, there is a paucity of long-term results of partial meniscectomy for degenerative MMPRTs.
UNASSIGNED: To 1) evaluate long-term patient-reported and radiographic outcomes of patients who underwent partial medial meniscectomy (PMM) for MMPRTs, and 2) determine the rate of and risk factors for conversion to total knee TKA.
UNASSIGNED: Case series; Level of evidence, 4.
UNASSIGNED: A previously identified cohort of 26 patients treated with partial meniscectomy for isolated MMPRTs between 2005 and 2013 was prospectively followed for long-term outcomes at a minimum 10-year follow-up. Patients were evaluated for International Knee Documentation Committee (IKDC) outcome score, reoperation, and conversion to TKA. Failure was defined as conversion to arthroplasty or a severely abnormal IKDC subjective score <75.4.
UNASSIGNED: This study included 26 patients (10 men, 16 women; mean age, 54 ± 8.7 years [range, 38-71 years] at diagnosis; body mass index, 32.9 ± 5.5) who were followed for a mean of 14.0 ± 3.6 years (range, 10.1-19.6 years). At the final follow-up, 1 patient was deceased and 18 (72%) of the remaining 25 patients had progressed to TKA, with 1 (4%) patient undergoing repeat meniscectomy. The 6 (24%) patients who had not progressed to TKA or revision surgery reported a mean IKDC score of 57 ± 23. Nineteen patients underwent subsequent surgery and 5 demonstrated severely abnormal IKDC scores resulting in a clinical failure rate of 96% (24 of the 25 living patients) at a mean 14-year follow-up.
UNASSIGNED: PMM for medial meniscus posterior horn root tears demonstrated 72% progression to TKA and 96% failure according to subjective clinical outcomes at a minimum 10-year follow-up.

BACKGROUND: In a previous study, the 84-day administration of glycosaminoglycans (GAGs), with or without native collagen type II (NC), in an osteoarthritis (OA)-induced rabbit model slowed down OA progression, improved several micro- and macroscopic parameters and magnetic resonance imaging (MRI) biomarkers in cartilage, and increased hyaluronic acid levels in synovial fluid. To elucidate the potential underlying mechanisms, a transcriptomics approach was conducted using medial femoral condyle and trochlea samples.
RESULTS: The administration of chondroitin sulfate (CS), glucosamine hydrochloride (GlHCl), and hyaluronic acid (HA), with (CGH-NC) or without (CGH) NC, strongly modulated several genes involved in chondrocyte extracellular matrix (ECM) remodeling and homeostasis when compared to non-treated rabbits (CTR group). Notably, both treatments shared the main mechanism of action, which was related to ECM modulation through the down-regulation of genes encoding proteolytic enzymes, such as ADAM metallopeptidase with thrombospondin type 1 motif, 9 (Adamts9), and the overexpression of genes with a relevant role in the synthesis of ECM components, such as aggrecan (Acan) in both CGH-NC and CGH groups, and fibronectin 1 (Fn1) and collagen type II, alpha 1 (Col2A1) in the CGH group. Furthermore, there was a significant modulation at the gene expression level of the mTOR signaling pathway, which is associated with the regulation of the synthesis of ECM proteolytic enzymes, only in CGH-NC-supplemented rabbits. This modulation could account for the better outcomes concerning the microscopic and macroscopic evaluations reported in these animals.
CONCLUSIONS: In conclusion, the expression of key genes involved in chondrocyte ECM remodeling and homeostasis was significantly modulated in rabbits in response to both CGH and CGH-NC treatments, which would partly explain the mechanisms by which these therapies exert beneficial effects against OA.

Articular cartilage phenotypic homeostasis is crucial for life-long joint function, but the underlying cellular and molecular mechanisms governing chondrocyte stability remain poorly understood. Here, we show that the protein tyrosine phosphatase SHP2 is differentially expressed in articular cartilage (AC) and growth plate cartilage (GPC) and that it negatively regulates cell proliferation and cartilage phenotypic program. Postnatal SHP2 deletion in Prg4+ AC chondrocytes increased articular cellularity and thickness, whereas SHP2 deletion in Acan+ pan-chondrocytes caused excessive GPC chondrocyte proliferation and led to joint malformation post-puberty. These observations were verified in mice and in cultured chondrocytes following treatment with the SHP2 PROTAC inhibitor SHP2D26. Further mechanistic studies indicated that SHP2 negatively regulates SOX9 stability and transcriptional activity by influencing SOX9 phosphorylation and promoting its proteasome degradation. In contrast to published work, SHP2 ablation in chondrocytes did not impact IL-1-evoked inflammation responses, and SHP2\'s negative regulation of SOX9 could be curtailed by genetic or chemical SHP2 inhibition, suggesting that manipulating SHP2 signaling has translational potential for diseases of cartilage dyshomeostasis.

T1 ρ and Quantitative Susceptibility Mapping (QSM) are evolving as substrates for quantifying the progressive nature of knee osteoarthritis.
UNASSIGNED: To evaluate the effects of spin lock time combinations on depth-dependent T1 ρ estimation, in adjunct to QSM, and characterize the degree of shared variance in QSM and T1 ρ for the quantitative measurement of articular cartilage.
UNASSIGNED: Twenty healthy participants (10 ​M/10F, 22.2 ​± ​3.4 years) underwent bilateral knee MRI using T1 ρ MAPPS sequences with varying TSLs ([0-120] ms), along with a 3D spoiled gradient echo for QSM. Five total TSL combinations were used for T1 ρ computation, and direct depth-based comparison. Depth-wide variance was assessed in comparison to QSM as a basis to assess for depth-specific variation in T1 ρ computations across healthy cartilage.
UNASSIGNED: Longer T1 ρ relaxation times were observed for TSL combinations with higher spin lock times. Depth-specific differences were documented for both QSM and T1 ρ , with most change found at ∼60% depth of the cartilage, relative to the surface. Direct squared linear correlation revealed that most T1 ρ TSL combinations can explain over 30% of the variability in QSM, suggesting inherent shared sensitivity to cartilage microstructure.
UNASSIGNED: T1 ρ mapping is subjective to the spin lock time combinations used for computation of relaxation times. When paired with QSM, both similarities and differences in signal sensitivity may be complementary to capture depth-wide changes in articular cartilage.

BACKGROUND: Estrogen deficiency and Diabetes mellitus (DM) cause joint tissue deterioration, although the mechanisms are uncertain. This study evaluated the immunoexpression of autophagy and NLRP3-inflammasome markers, in rat articular cartilage with estrogen deficiency and DM.
METHODS: Twenty rats were sham-operated (SHAM) or ovariectomized (OVX) and equally allocated into four groups: SHAM and OVX groups administered with vehicle solution; SHAM and OVX groups treated with 60 mg/kg/body weight of streptozotocin, intraperitoneally, to induce DM (SHAM-DM and OVX-DM groups). After seven weeks, the rats were euthanized, and their joint knees were processed for paraffin embedding. Sections were stained with haematoxylin-eosin, toluidine blue, safranin-O/fast-green or subjected to picrosirius-red-polarisation method; immunohistochemistry to detect beclin-1 and microtubule-associated protein 1B-light chain 3 (autophagy markers), NLRP3 and interleukin-1β (IL-1β) (inflammasome activation markers), along with matrix metalloproteinase-9 (MMP-9), Nuclear factor-kappa B (NFκB), and Vascular endothelial growth factor A (VEGF-A) were performed.
RESULTS: Deterioration of articular cartilage and subchondral bone were greater in SHAM-DM and OVX-DM groups. Higher percentages of immunolabeled chondrocytes to NLRP3, IL-1β, MMP-9, NFκB, and VEGF-A, as well as lower percentages of chondrocytes immunolabeled to autophagy markers, were noticed in estrogen-deficient and diabetic groups. These differences were greater in the OVX-DM group. Percentages of immunolabeled chondrocytes showed negative correlation between autophagy markers v.s IL-1β, NLRP-3, MMP-9, NFκB, and VEGF-A, along with positive correlation between VEGF-A vs. MMP-9, NFκB, IL-1β, and NLRP3, and MMP-9 vs. NFκB.
CONCLUSIONS: In conclusion, autophagy reduction and NLRP3 inflammasome activation in chondrocytes may be implicated in articular cartilage degradation, under estrogen-deficient and DM conditions. Moreover, the combination of estrogen deficiency and DM may potentiate those effects.

UNASSIGNED: Chondrocyte viability is associated with the clinical success of osteochondral allograft (OCA) transplantation.
UNASSIGNED: To investigate the effect of distal femoral OCA plug harvest and recipient site preparation on regional cell viability using traditional handheld saline irrigation versus saline submersion.
UNASSIGNED: Controlled laboratory study.
UNASSIGNED: For each of 13 femoral hemicondyles, 4 cartilage samples were harvested: (1) 5-mm control cartilage, (2) 15-mm OCA donor plug harvested with a powered coring reamer and concurrent handheld saline irrigation (\"traditional\"), (3) 15-mm OCA donor plug harvested while submerged under normal saline (\"submerged\"), and (4) 5-mm cartilage from the peripheral rim of a recipient socket created with a 15-mm cannulated counterbore reamer to a total depth of 7 mm with concurrent handheld saline irrigation (\"recipient\"). The 15 mm-diameter plugs were divided into the central 5 mm and the peripheral 5 mm (2 edges) for comparisons. Samples were stained using calcein and ethidium, and live/dead cell percentages were calculated and compared across groups.
UNASSIGNED: Compared with the submerged group, the traditional group had significantly lower percentages of live cells across the whole plug (71.54% ± 4.82% vs 61.42% ± 4.98%, respectively; P = .003), at the center of the plug (72.76% ± 5.87% vs 62.30% ± 6.11%, respectively; P = .005), and at the periphery of the plug (70.93% ± 4.51% vs 60.91% ± 4.75%, respectively; P = .003). The traditional group had significantly fewer live cells in all plug regions compared with the control group (77.51% ± 9.23%; P < .0001). There were no significant differences in cell viability between the control and submerged groups (whole: P = .590; center: P = .713; periphery: P = .799). There were no differences between the central and peripheral 5-mm plug regions for the traditional (62.30% ± 6.11% vs 60.91% ± 4.75%, respectively; P = .108) and submerged (72.76% ± 5.87% vs 70.93% ± 4.51%, respectively; P = .061) groups. The recipient group (61.10% ± 5.02%) had significantly lower cell viability compared with the control group (P < .0001) and the periphery of the submerged group (P = .009) but was equivalent to the periphery of the traditional group (P = .990).
UNASSIGNED: There was a significant amount of chondrocyte death induced by OCA donor plug harvesting using a powered coring reamer with traditional handheld saline irrigation, which was mitigated by harvesting the plug while the allograft was submerged under saline.
UNASSIGNED: Mitigating this thermally induced damage by harvesting the OCA plug while the allograft was submerged in saline maintained chondrocyte viability throughout the plug and may help to improve the integration and survival of OCAs.

Fourier transform infrared spectroscopy (FTIRS) can provide rich information on the composition and content of samples, enabling the detection of subtle changes in tissue composition and structure. This study represents the first application of FTIRS to investigate cartilage under microgravity. Simulated microgravity cartilage model was firstly established by tail-suspension (TS) for 7, 14 and 21 days, which would be compared to control samples. A self-developed hollow optical fiber attenuated total reflection (HOF-ATR) probe coupled with a FTIR spectrometer was used for the spectral acquisition of cartilage samples in situ, and one-way analysis of variance (ANOVA) was employed to analyze the changes in the contents of cartilage matrix at different stages. The results indicate that cartilage degenerates in microgravity, the collagen content gradually decreases with the TS time, and the structure of collagen fibers changes. The trends of proteoglycan content and collagen integrity show an initial decrease followed by an increase, ultimately significantly decreasing. The findings provide the basis for the cartilage degeneration in microgravity with TS time, which must be of real significance for space science and health detection.

UNASSIGNED: To investigate the ameliorative effect of tanshinone ⅡA (Tan) on osteoarticular degeneration in ovariectomized rats (a postmenopausal estrogen deficiency model) and the mechanisms involved.
UNASSIGNED: Eight-week-old female Sprague Dawley (SD) rats were randomly allocated to 5 groups (n=10 each), including a Sham operation group (Sham), an ovariectomy group (OVX), and low, medium, and high-dose Tan groups. Eight weeks after bilateral ovariectomy, the rats in the low, medium, and high-dose Tan groups were treated with Tan at the doses of 5, 10, and 20 mg/kg for a duration of 28 days. Evaluation of the rat articular cartilage was performed using X-ray imaging, anatomical observation, hematoxylin and eosin (H&E) staining, and toluidine blue staining. Immunohistochemistry was performed to assess the expression levels of transforming growth factor β1 (TGF-β1), phosphorylated-smad2 (p-Smad2), type Ⅱ collagen (CⅡ), matrix metalloproteinase 9 (MMP-9), and MMP-13 in the cartilage tissue.
UNASSIGNED: The knee joints of the OVX rats exhibited narrowed joint spaces, osteophyte formation, cartilage erosion or even localized cartilage cracks, faded methylene blue staining on the cartilage surface, disordered arrangement of chondrocytes, unclear or interrupted tidal line, and increased Kellgren-Lawrence grading, Pelletier grading, Mankin grading, and OARSI scores compared to those of the Sham group (P<0.01), as revealed by X-ray imaging, anatomical observation, and histological examination results. Tan ameliorated the degenerative changes in the knee joint caused by OVX in a dose-dependent manner while improving Kellgren-Lawrence grading, Pelletier grading, Mankin grading, and OARSI scores. Immunohistochemistry findings showed that TGF-β1, p-Smad2, and CⅡ expression levels were significantly increased (P<0.01), while MMP-9 and MMP-13 expression levels were significantly decreased (P<0.01) in the articular cartilage of the Tan group compared to those of the OVX group, with all these effects being dose-dependent.
UNASSIGNED: Tan mitigates articular cartilage degeneration in ovariectomized rats, which may be related to the regulation of TGF-β1/Smad2/MMPs signaling pathway.

UNASSIGNED: Mesenchymal stem cell (MSC) therapy has ameliorative effects for treating knee osteoarthritis (KOA) disease. Moreover, there is a growing interest in using MSCs-derived secretome (Sec) containing trophic factors secreted by MSCs for KOA treatment. Recently, some studies have suggested that the combination of MSCs and Sec has the potential to treat the diseases.
UNASSIGNED: This study aimed to evaluate the ameliorative effects of combined administration of infrapatellar fat pad (IPFP)-derived MSCs, a type of adipose-derived stem cells (ASCs), for treating degenerated cartilage in a rat model of KOA.
UNASSIGNED: IPFP-ASCs were isolated from the IPFP of male rats. Sec was obtained from IPFP-ASCs in the fourth passage. Eight weeks after the induction of KOA by collagenase II, the rats were divided into 5 groups (n=5), including a control group with no treatment, and four experimental groups that received sodium hyaluronate (Hyalgan®, Hya), ASCs, Sec, and IPFP-ASCs+Sec, respectively by an infrapatellar injection. To perform the pathological and radiological evaluations, the animals were sacrificed 8 weeks later.
UNASSIGNED: Our findings indicated that combined administration of the IPFP-ASCs and Sec statistically (P<0.05) improved scores of medial tibial and femoral condyles and medial fabella osteophytes. Also, it statistically (P<0.05) enhances the cartilage surface, matrix, cell distribution and population viability, and subchondral bone indices. No statistical difference was observed between IPFP-ASCs+Sec and IPFP-ASCs.
UNASSIGNED: Administration of IPFP-ASCs+Sec has a therapeutic potential to treat KOA in rats. However, there is no difference in the combined administration of IPFP-ASCs and Sec with IPFP-ASCs alone.