Factors associated with meniscus volume in knees free of degenerative features.

OBJECTIVES: To explore factors that were associated with meniscus volume in knees free of radiographic osteoarthritis (OA) features and symptoms of OA. METHODS: In the third Rotterdam Study cohort, clinical, radiographic, and magnetic resonance data were obtained at baseline (BL) and after 5 years of follow-up. Meniscus volumes and their change over time were calculated after semi-automatic segmentation on Magnetic Resonance Imaging. Knees with radiographic OA features (Kellgren and Lawrence>0) or clinical diagnosis of OA (American College of Rheumatology) at BL were excluded. Ten OA risk factors were adjusted in the multivariable analysis (generalized estimating equations), treating two knees within subjects as repeated measurements. RESULTS: From 1065 knees (570 subjects), the average (standard deviation) age and Body mass index (BMI) of included subjects were 54.3 (3.7) years and 26.5 (4.4) kg/m2. At BL, nine factors (varus alignment, higher BMI, meniscus pathologies, meniscus extrusion, cartilage lesions, injury, greater physical activity level, quadriceps muscle strength, and higher age) were significantly associated with greater meniscus volume. Five factors (injury, meniscus pathologies, meniscus extrusion, higher age, and change of BMI) were significantly associated with meniscus volume loss. CONCLUSIONS: Modifiable factors (varus alignment, BMI, physical activity level, and quadriceps muscle strength) and non-modifiable factors (higher age, injury, meniscus pathologies, meniscus extrusion, and cartilage lesions) were all associated with meniscus volume or meniscus volume loss over time.

Autologous menisci-cruciate ligament composite as a flap for soft tissue reconstruction following malignant bone tumor resection around the knee.

BACKGROUND: Despite significant improvements in oncological treatment, the management of soft tissue defects following malignant tumor resection remains challenging. We investigated whether autologous menisci and cruciate ligament, which are traditionally discarded, can be recycled as a supplemental flap in repairing soft tissue defects following malignant bone tumor resection and endoprosthetic reconstruction around the knee. METHODS: Four knee specimens were dissected to provide a basis for the design of the menisci-cruciate ligament composite. Then, 40 patients with bone malignancies around the knee were enrolled and underwent reconstruction with free or vascularized composite following malignant tumor resection. The clinical, radiographic, and functional outcomes of this technique were evaluated in >1-year follow-up in each patient and compared with 87 patients who suffered from bone malignancies around the knee and were treated by limb salvage but without composite at our center over the same period. During the follow-up, a composite from one patient who underwent secondary amputation was retrieved and examined for in vivo remodeling. RESULTS: Fourteen patients were treated with vascularized composite transfer (10 distal femurs and 4 proximal tibias) and 26 patients with free composite transfer (19 distal femurs and 7 proximal tibias). The composite can be used to cover the area of soft tissue defect from 22 to 48.38 cm2 (34.67 ± 6.48 cm2 ). With contrast-enhanced ultrasound, peripheral rim healing and dotted blood flow signal at the side of anastomosis were detected on a patient 16 months after free composite transfer. Gross macroscopic remodeling and histopathologic analysis of a retrieved composite also indicated good healing with surrounding tissues and living cells in the composite. The complications and oncologic outcomes were comparable between study and control cohorts, but better Musculoskeletal Tumor Society (MSTS) score for patients reconstructed with composite (26.68 vs. 25.66, p  = 0.004). Of note, MSTS score was higher for patients reconstructed with composite at distal femur subdivision compared with the same subdivision in the control cohort (26.97 vs. 25.90, p  = 0.009). No statically significant difference was noted in complications, oncologic, and functional outcomes for patients reconstructed with free or vascularized composite. CONCLUSION: Autogenous menisci-cruciate ligament composite is an alternative option for soft tissue reconstruction. Either vascularized or free composite can be applied, depending on the size and localization of the defect.

3D analysis and grading of calcifications from ex vivo human meniscus.

OBJECTIVE: Meniscal calcifications are associated with the pathogenesis of knee osteoarthritis (OA). We propose a micro-computed tomography (µCT) based 3D analysis of meniscal calcifications ex vivo, including a new grading system. METHOD: Human medial and lateral menisci were obtained from 10 patients having total knee replacement for medial compartment OA and 10 deceased donors without knee OA (healthy references). The samples were fixed; one subsection was imaged with µCT, and the adjacent tissue was processed for histological evaluation. Calcifications were examined from the reconstructed 3D µCT images, and a new grading system was developed. To validate the grading system, meniscal calcification volumes (CVM) were quantitatively analyzed and compared between the calcification grades. Furthermore, we estimated the relationship between histopathological degeneration and the calcification severity. RESULTS: 3D µCT images depict calcifications in every sample, including diminutive calcifications that are not visible in histology. In the new grading system, starting from grade 2, each grade results in a CVM that is 20.3 times higher (95% CI 13.3-30.5) than in the previous grade. However, there was no apparent difference in CVM between grades 1 and 2. The calcification grades appear to increase with the increasing histopathological degeneration, although histopathological degeneration is also observed with small calcification grades. CONCLUSIONS: 3D µCT grading of meniscal calcifications is feasible. Interestingly, it seems that there are two patterns of degeneration in the menisci of our sample set: 1) with diminutive calcifications (calcification grades 1-2), and 2) with large to widespread calcifications (calcification grades 3-5).

Effect of Extensor Muscle Strength on Meniscus Damage Progression in Subjects Without Radiologic Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

BACKGROUND: It has been demonstrated that high extensor strength decreases knee osteoarthritis symptomatic progression. However, few studies have detected a significant association between extensor strength and structural progression. METHODS: Participants in the Osteoarthritis Initiative with both muscle strength and meniscus assessment, Kellgren-Lawrence grade 1 or less, and body mass index less than 30 were enrolled. In a separate-sex analysis, participants were divided into the high and low strength groups, referring to the median value. Meniscus progression according to the Magnetic Resonance Imaging Osteoarthritis Knee Score was compared between the two groups at 12 mos (393 females and 229 males) and 24 mos (340 females and 208 males). RESULTS: In females, less overall medial meniscus progression (11.1% [17/153] vs. 23.2% [32/138], P = 0.04), less medial meniscal medial extrusion (5.2% [8/155] vs. 12.5% [18/144], P = 0.04), and less medial meniscal anterior extrusion progression (0% [0/108] vs. 5.3% [6/113], P = 0.03) were present in the high strength group at 24 mos. In males, no significant difference was detected between the high strength group and the low strength group. CONCLUSIONS: In females, higher extensor muscle strength was associated with a decreased risk of medial meniscus progression in medial and anterior extrusion.

Age alters gait compensations following meniscal injury in male rats.

With age, susceptibility to osteoarthritis (OA) and OA-related pain and disability increases. Like in OA patients, gait patterns in rodent OA models shift to protect the injured limb during loading. However, unlike in OA patients, it is unknown how age affects gait changes in rodent OA models. In this study, gait compensations following meniscal injury in 3-, 6-, and 9-month-old rats were evaluated to examine age-effects of OA-related joint dysfunction. Rats 3, 6, and 9 months received medial collateral ligament transection plus medial meniscus transection (MCLT + MMT) surgery (n = 8/age group) or a skin incision (n = 8/age group). Postsurgery, rats underwent gait testing at 2, 4, 6, and 8 weeks. Postmortem, joints were processed for histology to assess cartilage damage. MCLT + MMT rats walked with reduced vertical loading in their injured limbs immediately after injury and throughout OA progression. Compared to sham-operated limbs, 6- and 9-month MCLT + MMT animals reduced loading in their injured limbs while 3-month MCLT + MMT animals did not. MCLT + MMT rats also increased stance time on the injured limb compared to the contralateral limb. Additionally, for the MCLT + MMT animals, 6- and 9-month animals had significantly worse cartilage damage compared to 3-month animals. These data indicated age at injury onset affects how animals load the OA-affected joint, with older animals developing gait compensations that more markedly reduce weight on the injured limb during walking.

Selective Unique Signs of Meniscus Tears as Visualized by Magnetic Resonance Imaging.

ABSTRACT: The meniscus is an organized collection of fibrocartilaginous tissue that is located between the femoral condyles and the tibial plateau of the knee which primarily assists with load transmission. The complex composition of articulating soft-tissue structures in the knee causes the menisci to become a common source of injury, especially in the realm of athletic trauma. Magnetic resonance imaging (MRI) has become the imaging modality of choice for evaluating patients with suspected meniscal pathology because of its numerous advantages over plain radiographs. Most forms of meniscal tears have classic MRI findings and are used in correlation with physical examination findings to confirm or rule out a diagnosis. These imaging findings are referred to as signs and have been well studied, and the associated eponyms for each sign are well published throughout the literature. This article will review and describe a unique selection of meniscal pathology as visualized by MRI that is more commonly published in musculoskeletal radiology literature when compared with orthopedics and sports medicine literature.

Histologic and molecular features in pathologic human menisci from knees with and without osteoarthritis.

The objective of this study was to evaluate histologic and molecular features of meniscus degeneration in cohorts of patients with and without osteoarthritis (OA) of the knee. Menisci were obtained from patients undergoing total knee arthroplasty for OA (TKA) or arthroscopic partial meniscectomy (APM) for a torn knee meniscus. Degenerative meniscal tears were among the most common tear type in the APM group based on the pattern. Using an integrative workflow for molecular evaluation of formalin-fixed and paraffin-embedded tissues, human menisci underwent blinded histologic evaluation and NanoString gene expression analyses. Histology revealed increased proteoglycan content in TKA menisci compared to APM menisci, but otherwise no significant differences in the total pathology score or sub-scores between patients based on age or cohort. NanoString analyses revealed differential expression of genes primarily associated with the PI3K-AKT signaling pathway, cell cycle, and apoptosis. These data provide new insights into histological and molecular features of meniscus degeneration in patients with and without knee OA. Histologic assessment of menisci showed similar severity of overall degeneration between cohorts, but there were differences at the molecular level. The dysregulated pathways identified in this study could contribute to early-onset meniscus degeneration, or to a predisposition to meniscus tears and subsequent knee OA. Further studies that validate genes and pathways uncovered in this study will allow us to evaluate novel approaches to assess and treat meniscal degeneration.

A pilot study to assess the healing of meniscal tears in young adult goats.

Meniscal tears are a common orthopedic injury, yet their healing is difficult to assess post-operatively. This impedes clinical decisions as the healing status of the meniscus cannot be accurately determined non-invasively. Thus, the objectives of this study were to explore the utility of a goat model and to use quantitative magnetic resonance imaging (MRI) techniques, histology, and biomechanical testing to assess the healing status of surgically induced meniscal tears. Adiabatic T1ρ, T2, and T2* relaxation times were quantified for both operated and control menisci ex vivo. Histology was used to assign healing status, assess compositional elements, and associate healing status with compositional elements. Biomechanical testing determined the failure load of healing lesions. Adiabatic T1ρ, T2, and T2* were able to quantitatively identify different healing states. Histology showed evidence of diminished proteoglycans and increased vascularity in both healed and non-healed menisci with surgically induced tears. Biomechanical results revealed that increased healing (as assessed histologically and on MRI) was associated with greater failure load. Our findings indicate increased healing is associated with greater meniscal strength and decreased signal differences (relative to contralateral controls) on MRI. This indicates that quantitative MRI may be a viable method to assess meniscal tears post-operatively.

Wnt5a/Platelet-rich plasma synergistically inhibits IL-1ß-induced inflammatory activity through NF-κB signaling pathway and prevents cartilage damage and promotes meniscus regeneration.

Noncanonical Wnt5a is a particularly attractive growth factor to maintain chondrogenesis. Platelet-rich plasma (PRP) is an autologous blood-derived product and a source of bioactive growth factors involved in tissue regeneration. The present study aimed to investigate the effect and inflammation reaction of Wnt5a/PRP on meniscus cells, and evaluate meniscus regeneration and osteoarthritis (OA) prevention by the application of Wnt5a/PRP gel in a rabbit model of massive meniscal defect. In vitro, the proliferation, migration, differentiation, and interleukin-1 beta (IL-1ß) IL-1ß-induced inflammation reaction of meniscus cells treated by Wnt5a and PRP was assessed. In vivo, the anterior half of the medial meniscus of 18 New Zealand rabbits was excised and implanted with PRP gel, Wnt5a/PRP gel or untreated. After 6 and 12 weeks, the regenerated meniscus were evaluated. Wnt5a can promote the migration of meniscus cells. PRP and Wnt5a had synergistic effect in promoting the proliferation and chondrogenic differentiation of meniscus cells. The IL-1ß-induced meniscus cells study showed that PRP and Wnt5a had the anti-inflammatory actions through nuclear factor kB (NF-κB) signaling pathway. PRP and Wnt5a/PRP significantly inhibited the increase of the p-p65/p65 and p-IκB-α/IκB-α ratios. In vivo transplantation of Wnt5a/PRP gel was demonstrated to promote meniscus regeneration, while reducing OA of knee joint. Wnt5a with PRP had the anti-inflammatory activity in an IL-1ß-induced inflammatory model. They can synergistically improve the chondorgenic differentiation of meniscus cells. Wnt5a/PRP gel treatment could potentially be developed into a new method for meniscus regeneration and the prevention of OA.

3D-bioprinting ready-to-implant anisotropic menisci recapitulate healthy meniscus phenotype and prevent secondary joint degeneration.

Objectives: Disruption of anisotropic phenotypes of the meniscus would contribute to OA progression. Exploring phenotype changes of the anisotropic meniscus in joint degeneration would help understand the biologic interaction between the meniscus and OA, and further facilitate the therapeutic strategies of meniscus injury-related joint degeneration. Meanwhile, engineering biomimetic meniscal tissue mimicking the anisotropy of the healthy meniscus remains a challenge. Methods & Results: Meniscal disruption of phenotype anisotropy (PBV growth, cellular phenotype and ECM depositions) was confirmed in OA patient samples. To recapitulate healthy meniscus phenotypes, 3D-bioprinted anisotropic TCM meniscus constructs with PBV growth and regional differential cell and ECM depositions were generated. Transplanted 3D-bioprinted meniscus into rabbit knees recapitulated phenotypes of native healthy meniscus and conferred long-term protection against secondary joint degeneration. Conclusion: 3D-bioprinted TCM meniscus not only restored the anisotropy of native healthy meniscus with PBV infiltration and better shape retention, but better maintained joint function and prevented secondary joint degeneration, which provided a new strategy for the clinical treatment of meniscus injury-related joint degenerative diseases.

The efficacy of meniscus posterior root tears repair: A systematic review and meta-analysis.

PURPOSE: To report of efficacy repair treatment for meniscus posterior root tears repair. METHODS: We systematically searched databases including PubMed, Embase, and Cochrane Library for relevant articles. Coleman Methodology Score was used for a quality assessment of the included studies. A meta-analysis was performed to analyze for efficacy of MMPRTs repair. RESULTS: Twenty-two studies, 14 level III and 8 level IV, were included in this systematic review, with a total of 926 cases. Studies comparing repair with either meniscectomy or conservative treatment found greater improvement and slower progression of Kellgrene-Lawrence grade with meniscal repair. Decreased meniscus extrusion is beneficial to the prognosis of patients undergoing MMPRTs repair. As treatment efficacy, the Lysholm score increased 28.87 (P < 0.001), IKDC score increased 31.73. The overall pooled event rates of progression of K-L grade is 0.200. Difference of Lysholm score and IKDC score between repair and meniscectomy were 8.72 and 9.67. CONCLUSIONS: The clinical subjective score after MMPRT repair was significantly improved compared with the preoperative status. Considering the progression of joint K-L grade, it can prevent the progression of arthrosis to some extent, but not completely. Decreased meniscus extrusion is beneficial to the prognosis of patients undergoing MMPRTs repair. Based on these results, MMPRTs repair cloud result favorable outcomes.

Gene expression profiling of primary fibrochondrocyte cultures in traumatic and degenerative meniscus lesions.

PURPOSE: This study aimed to investigate how fibroblastic and chondrocytic properties of human meniscal fibrochondrocytes are affected in culture conditions according to the type of meniscal pathology and localization, and to provide basic information for tissue-engineering studies. METHODS: Primary fibrochondrocyte cultures were prepared from meniscus samples of patients who had either traumatic tear or degeneration due to osteoarthritis. Cultures were compared in terms of mRNA expression levels of COL1A1, COL2A1, COMP1, HIF1A, HIF2A, and SOX9 and secreted total collagen and sulfated sGAG levels according to the type of meniscal pathology, anatomical localization, and the number of subcultures. RESULTS: mRNA expression levels of COL1A1, COMP1, HIF1A, HIF2A, and SOX9 were found to be increased in subsequent subcultures in all specimens. COL1A1 mRNA expression levels of both lateral and medial menisci of patients with traumatic tear were significantly higher than in patients with degenerative pathology, indicating a more fibroblastic character. P1 subculture of lateral and P3 or further subculture of medial meniscus showed more fibroblastic characteristics in patients with degenerative pathology. Furthermore, in patients with degenerative pathology, the subcultures of the lateral meniscus (especially on the inner part) presented more chondrocytic characteristics than did those of medial meniscus. CONCLUSIONS: The mRNA expression levels of the cultures showed significant differences according to the anatomical localization and pathology of the meniscus, indicating distinct chondrocytic and fibroblastic features. This fundamental knowledge would help researchers to choose more efficient cell sources for cell-seeding of a meniscus scaffold, and to generate a construct resembling the original meniscus tissue.

Degeneration of the articular disc in the human triangular fibrocartilage complex.

INTRODUCTION: Traumatic injuries of the triangular fibrocartilage complex (TFCC) are frequent reasons for ulnar wrist pain. The assessment of the extent of articular disc (AD) degeneration is important for the differentiation of acute injuries versus chronic lesions. MATERIALS AND METHODS: The AD of the TFCC of eleven human cadaver wrists was dissected. Degeneration was analyzed according to the grading of Krenn et al. Hematoxylin-eosin was used to determine the tissue morphology. Degeneration was evaluated using the staining intensity of alcian blue, the immunohistochemistry of the proteoglycan versican and the immunoreactivity of NITEGE, an aggrecan fragment. RESULTS: The staining homogeneity of HE decreased with higher degeneration of the AD and basophilic tissue areas were more frequently seen. Two specimens were characterized as degeneration grade 1, five specimens as grade 2, and four specimens as grade 3, respectively. Staining intensity of alcian blue increased with higher degeneration grade of the specimens. Immunoreactivity for NITEGE was detected around tissue fissures and perforations as well as matrix splits. Immunoreactivity for versican was found concentrated in the tissue around matrix fissures and lesions as well as loose connective tissue at the ulnar border of the AD. Specimens with degeneration grade 2 had the strongest immunoreactivity of NITEGE and versican. Cell clusters were observed in specimens with degeneration grade 2 and 3, which were stained by alcian blue and immunoreactive for NITEGE and versican. Increasing age of the cadaver wrists correlated with a higher degree of degeneration (p < 0.0001, r = 0.68). CONCLUSIONS: The fibrocartilage of degenerated ADs contains NITEGE and versican. The amount of the immunoreactivity of these markers allows the differentiation of degenerative changes into three grades. The degeneration of the AD increases with age and emphasizes its important mechanical function.

Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study.

OBJECTIVE: To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard. METHODS: Consecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0-3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other's findings. RESULTS: 11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%-sensitivity of 91% (range 71%-87% in single sites) and specificity of 59% (range 68%-92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation. CONCLUSION: Ultrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.

PTH1-34 inhibited TNF-α expression and antagonized TNF-α-induced MMP13 expression in MIO mice.

This study aims to investigate the effects and mechanisms of parathyroid hormone [1-34] (PTH1-34) on TNF-α-stimulated mice chondrocytes, as well as cartilage from a meniscus injury induced osteoarthritis (MIO) mice model. The C57BL/6J mice received medial meniscectomy, and then administrated with PTH1-34. The results showed that PTH1-34 administration decreased secondary allodynia and the pain-related transcripts. The IHC, ELISA, Micro-CT imaging and histopathology analysis revealed the significantly improved subchondral plate thickness and bone porosity, the reduced pro-inflammatory cytokines in serum and joint fluid. In vitro, mice chondrocyte was treated with TNF-α or co-cultured with synovial cells. The results showed that TNF-α markedly upregulated the MMP13 expression, and the ERK1/2, NF-κB or PI3K signaling pathway inhibitors could reverse the induction effect of TNF-α on expression of MMP13 in chondrocytes. PTH1-34 alone has no effect on the expression of MMP13 and NF-κB signaling pathways, but the PTH1-34 could reverse the induction effect of TNF-α on MMP13 expression and NF-κB signaling pathway activation in chondrocytes. In addition, PTH1-34 administration inhibited the expression of TNF-α and MMP13, and chondrocyte viability, while the PKA repressor reversed the effect of PTH1-34 in chondrocytes co-cultured with synovial cells. In conclusion, PTH1-34 has an obvious analgesic and anti-inflammatory effect, inhibits the matrix synthesis and alleviates the progression of osteoarthritis. In vitro, PTH1-34 inhibited TNF-α expression and antagonized TNF-α-induced MMP13 expression via the PKA pathway and the NF-κB signaling pathways, respectively.

Association between meniscal volume and development of knee osteoarthritis.

OBJECTIVE: To assess the association between meniscal volume, its change over time and the development of knee OA after 30 months in overweight/obese women. METHODS: Data from the PRevention of knee Osteoarthritis in Overweight Females study were used. This cohort included 407 women with a BMI ≥ 27 kg/m2, free of OA-related symptoms. The primary outcome measure was incident OA after 30 months, defined by one out of the following criteria: medial or lateral joint space narrowing (JSN) ≥ 1.0 mm, incident radiographic OA [Kellgren and Lawrence (K&L) ≥ 2], or incident clinical OA. The secondary outcomes were either of these items separately. Menisci at both baseline and follow-up were automatically segmented to obtain meniscal volume and delta-volumes. Generalized estimating equations were used to evaluate associations between the volume measures and the outcomes. RESULTS: Medial and lateral baseline and delta-volumes were not significantly associated to the primary outcome. Lateral meniscal baseline volume was significantly associated to lateral JSN [odds ratio (OR) = 0.87; 95% CI: 0.75, 0.99], while other measures were not. Medial and lateral baseline volume were positively associated to K&L incidence (OR = 1.32 and 1.22; 95% CI: 1.15, 1.50 and 1.03, 1.45, respectively), while medial and lateral delta-volume were negatively associated to K&L incidence (OR = 0.998 and 0.997; 95% CI: 0.997, 1.000 and 0.996, 0.999, respectively). None of the meniscal measures were significantly associated to incident clinical OA. CONCLUSION: Larger baseline meniscal volume and the decrease of meniscal volume over time were associated to the development of structural OA after 30 months in overweight and obese women.

An animal model study on the gene expression profile of meniscal degeneration.

Meniscal degeneration is a very common condition in elderly individuals, but the underlying mechanisms of its occurrence are not completely clear. This study examines the molecular mechanisms of meniscal degeneration. The anterior cruciate ligament (ACL) and lateral collateral ligament (LCL) of the right rear limbs of seven Wuzhishan mini-pigs were resected (meniscal degeneration group), and the left rear legs were sham-operated (control group). After 6 months, samples were taken for gene chip analysis, including differentially expressed gene (DEG) analysis, gene ontology (GO) analysis, clustering analysis, and pathway analysis. The selected 12 DEGs were validated by real time reverse transcription-polymerase chain reaction (RT-PCR). The two groups showed specific and highly clustered DEGs. A total of 893 DEGs were found, in which 537 are upregulated, and 356 are downregulated. The GO analysis showed that the significantly affected biological processes include nitric oxide metabolic process, male sex differentiation, and mesenchymal morphogenesis, the significantly affected cellular components include the endoplasmic reticulum membrane, and the significantly affected molecular functions include transition metal ion binding and iron ion binding. The pathway analysis showed that the significantly affected pathways include type II diabetes mellitus, inflammatory mediator regulation of TRP channels, and AMPK signaling pathway. The results of RT-PCR indicate that the microarray data accurately reflects the gene expression patterns. These findings indicate that several molecular mechanisms are involved in the development of meniscal degeneration, thus improving our understanding of meniscal degeneration and provide molecular therapeutic targets in the future.

Mesenchymal Stem Cells in Synovial Fluid Increase in Knees with Degenerative Meniscus Injury after Arthroscopic Procedures through the Endogenous Effects of CGRP and HGF.

BACKGROUND: Mesenchymal stem cells (MSCs) in synovial fluid increase after traumatic meniscus injuries. However, MSC kinetics in synovial fluid may differ for knees with degenerative meniscus injuries. Furthermore, the combination of surgical repair and synovial MSC transplantation has been found to improve clinical symptoms in patients with degenerative meniscus injury, and in this treatment, only the operation procedure without MSC transplantation might increase MSCs in synovial fluid; if so, soluble factors in synovial fluid will be involved. The purpose is this study was to examine whether MSCs exist in synovial fluid of knees with degenerative meniscus injury, to investigate whether MSCs in synovial fluid increase after harvest of synovium and meniscus repair, and to explore what soluble factors in synovial fluids affect the number of MSCs in synovial fluid. METHODS: Subjects were 7 patients with degenerative meniscus injury who underwent meniscal repair and synovial MSC transplantation. Synovial fluid (Pre) was aspirated from knees before harvest of synovium and meniscus repair. After 2 weeks, synovial fluid (Post) was aspirated again before transplantation of synovial MSCs. A half volume of the synovial fluid was plated and cultured for 2 weeks to count the colony formation. The other half was used for antibody array analysis, and the correlation coefficients between the signal intensity and colony number were measured in 503 factors. Factors with high correlation coefficients were verified by migration assay. RESULTS: While cell colonies derived from synovial fluid (Pre) were hardly observed, greater numbers of colonies from synovial fluid (Post) were demonstrated. Of the 503 factors, calcitonin gene-related peptide (CGRP) and hepatocyte growth factor (HGF) had high correlation coefficients between colony number and expression level. Both CGRP and HGF promoted migration of synovial fluid MSCs. CONCLUSIONS: MSCs in synovial fluid were hardly seen in knees with degenerated meniscus injury. They significantly increased 2 weeks after harvest of synovium and meniscus repair. Both CGRP and HGF in synovial fluid can possibly induce MSCs from synovium into synovial fluid. Graphical abstract.

The underlying mechanism of partial anterior cruciate ligament injuries to the meniscus degeneration of knee joint in rabbit models.

BACKGROUND: The diagnosis, treatment, and efficacy evaluation of anterior cruciate ligament (ACL) partial rupture remains controversial. This research aims to investigate the underlying mechanism of partial ACL injuries to the meniscus degeneration in the rabbit knee. METHODS: Sixty New Zealand white rabbits were randomly divided into three groups including an experimental group, a sham group (n = 6), and a blank control group (n = 6). The experimental group is composed of an anteromedial bundle (AMB) rupture group (n = 24) and a posterolateral bundle (PLB) rupture group (n = 24). Rabbits in the experimental group were subjected to right hind limbs knee surgery to induce ACL part injury under the arthroscopy. Finally, eight rabbits including 6 in the model group and 2 in the control group were sampled randomly on the 2nd, 4th, and 8th weeks respectively. We observed the typical form of the meniscus through HE staining. Expressions of inflammatory factors including interleukin-1ß (IL-1ß) and IL-17 in the knee joint fluid were determined by means of an ELISA. Analysis of the mRNA expressions of matrix metalloproteinases-13(MMP-13) was performed to evaluate the inflammatory mediators in the pathogenesis of the meniscus. RESULTS: HE staining results showed that the surface was rough and the tissues were loose displaying collagen fibers of varying thickness. Both IL-1ß and IL-17 in the synovial fluid and the positive rate of MMP-13 in addition to MMP-13 mRNA showed a demonstrable increase treads from the 2nd to the 8th week. The significant difference was found (P < 0.05) compared to the control group. CONCLUSION: We conclude that the elevated levels of IL-1ß and IL-17, along with increased MMP13 expression, resulted in meniscus degradation in the rabbit knee joint model with partial ACL injury.

Intra-articular corticosteroid knee injection induces a reduction in meniscal thickness with no treatment effect on cartilage volume: a case-control study.

Although intra-articular corticosteroid injections (IACI) are commonly used for the treatment of knee osteoarthritis (OA), there is controversy regarding possible deleterious effects on joint structure. In this line, this study investigates the effects of IACI on the evolution of knee OA structural changes and pain. Participants for this nested case-control study were from the Osteoarthritis Initiative. Knees of participants who had received an IACI and had magnetic resonance images (MRI) were named cases (n = 93), and each matched with one control (n = 93). Features assessed at the yearly visits and their changes within the follow-up period were from MRI (cartilage volume, meniscal thickness, bone marrow lesions, bone curvature, and synovial effusion size), X-ray (joint space width), and clinical (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain score) data. Participants who received IACI experienced a transient and significantly greater rate of loss of the meniscal thickness (p = 0.006) and joint space width (p = 0.011) in the knee medial compartment in the year they received the injection, compared to controls. No significant effect of the IACI was found on the rate of cartilage loss nor on any other knee structural changes or WOMAC pain post-treatment. In conclusion, a single IACI in knee OA was shown to be safe with no negative impact on structural changes, but there was a transient meniscal thickness reduction, a phenomenon for which the clinical relevance is at present unknown.