CARTILAGE

Cell-based cartilage repair is limited by loss of chondrogenic potential during in vitro expansion. Fibronectin (FN)-based selection may enrich progenitor-like cells with better matrix-forming ability, but its long-term effect on ECM production by hiPSC-derived chondroprogenitors (hiCPCs), their derived chondrocytes (hiCHOs), and primary articular chondrocytes (hACs) from lesioned or preserved areas remains unclear.

We here compared cartilage ECM formation by hiCPCs/hiCHO’s and hACs, with or without FN selection, over extended passaging using 3D organoids. Histology and quantitative image analysis were performed to assess tissue quality across passages.

Chondrogenicity in hiCPCs transiently improved early-stage ECM production upon FN-based selection, but accelerated loss of chondrogenicity was seen in later passages. This was evidenced by diminished matrix staining and structural degradation from passage 4 onward. In contrast, hACs from both preserved and lesioned cartilage maintained stable matrix-forming ability across passages, independent of FN-based selection.

FN-based selection does not preserve long-term chondrogenicity in hiCHOs and may even impair it during extended culture. In contrast, primary cell sources, regardless of cartilage integrity, demonstrate greater and robust chondrogenic capacity without requiring progenitor enrichment. These findings highlight the intrinsic ability of hACs and question the utility of FN-based selection in cartilage tissue engineering.

This study investigated the dose-dependent cytotoxicity and immunomodulatory effects of intra-articular local anaesthetics (lidocaine, mepivacaine, levobupivacaine) and corticosteroids (dexamethasone, methylprednisolone, methylprednisolone acetate) on canine fibroblast-like synoviocytes (FLS) in vitro. We evaluated cell viability and the expression of IL-6 and MMP-9.

Canine FLS were exposed to increasing concentrations of intra-articular agents. Cell viability was determined via MTT assays. Immunomodulatory effects were assessed via ELISA for IL-6 and gelatin zymography for MMP-9 activity after TNF-α stimulation with IC₅₀ concentrations.

All agents exhibited dose-dependent cytotoxicity. Dexamethasone was most cytotoxic (IC₅₀ ≈ 3.4×10^-4 mg/mL) but selectively inhibited TNF-α-induced MMP-9 activity without affecting IL-6 or inducing cytotoxicity at its IC₅₀. Mepivacaine significantly inhibited MMP-9 activity by 40% at 1 mg/mL and uniquely induced IL-6 in unstimulated cells. Lidocaine, methylprednisolone, and methylprednisolone acetate suppressed TNF-α-induced IL-6 expression.

Commonly used intra-articular agents induce dose-dependent cytotoxic effects on canine FLS at clinically relevant concentrations. This study provides the first evidence of species-specific responses for mepivacaine, levobupivacaine, and dexamethasone in canine FLS, highlighting mediator-specific and concentration-dependent effects crucial for optimizing intra-articular therapies in veterinary and translational medicine.

Lesions of adult articular cartilage occur due to trauma or disease, such as osteoarthritis. If they do not penetrate the subchondral bone, they are called partial-thickness defects (PTDs), which are believed not to heal. However, some reports indicate that minor PTDs can be repaired. We hypothesize that a critical-size PTD exists below which spontaneous healing occurs.

In an adult pig model, we created PTDs of minimal width (a scalpel cut) and systematically increased their width up to 0.5 mm. Defect analyses were conducted at 1 and 3 months post-surgery using light microscopy and histomorphometry.

None of the defects healed by repair cartilage; therefore, all PTDs are of a critical size. Surprisingly, a critical defect-size range was identified where significant mesenchymal tissue (MT) formation occurs, specifically in defects measuring 50-100 μm in width. The presence of this MT was limited to a 1-month time window. Furthermore, physiological joint loading during the postsurgical phase was associated with substantial structural tissue deformation, often leading to an overlapping of the side walls of the smallest defects. This results in a pseudo-covering of the defect void, which may thus be invisible when observed from above.

The main novel finding of this study is that there is no critical width below which PTDs undergo repair.

Damage to the joint-surface repair itself as fibrocartilage, a mixture of cartilaginous and fibrous tissues, which leads to debilitating conditions with persistent joint pain. The regulatory mechanisms that control the formation of these tissues are poorly understood.

We analyzed single-cell RNA-sequencing data from the repaired tissue formed in a chondral defect model of the monkey knee joint to identify genes specifically expressed in the repaired tissue. We used primary chondrocytes from semaphorin 7A (Sema7A) knockout mice to analyze the function of Sema7A in the dedifferentiation of chondrocytes in vitro. We introduced articular cartilage defect model in the knee joints in Sema7A knockout mice.

Single-cell RNA-sequencing analysis revealed that Sema7A is specifically expressed in the cartilaginous tissue in the repaired tissue formed in the articular cartilage defect. In vitro analysis showed that Sema7A autonomously induced the dedifferentiation of chondrocytes at passage 2, which is assumed to correspond to cartilaginous tissue cells, toward a fibroblastic state. In addition, Sema7A heteronomously suppressed the re-differentiation of passage 8 fibroblastic cells, which were assumed to correspond to fibrous tissue cells. Addition of anti-integrin β1 neutralizing antibody abolished Sema7A-induced suppression of Col2a1 and Col9a1 expression, suggesting that integrin β1 mediates Sema7A function. Sema7A knockout mice showed significantly improved healing in an articular surface defect model of the knee joints. Sema7A deletion increased cartilaginous tissue formation and decreased fibrous tissue formation in joint-surface defects.

Sema7A regulates the balance between cartilaginous and fibrous tissues during articular cartilage damage repair.

To systematically synthesize clinical, structural, biomarker, and safety outcomes of knee joint distraction (KJD) and implantable medial compartment shock absorbers (ISA) for tibiofemoral knee osteoarthritis (KOA), and to summarize comparative evidence versus arthroplasty, high tibial osteotomy (HTO), orthoses, and non-operative care.

A PRISMA-based systematic review of PubMed, EMBASE, Scopus, and Cochrane Library from inception to 1 October 2025 identified peer-reviewed clinical studies of KJD or ISA for tibiofemoral KOA. Two reviewers independently screened records, extracted data, and assessed risk of bias. Owing to substantial clinical and methodological heterogeneity and overlapping cohorts, a narrative synthesis was prespecified and no quantitative meta-analysis was performed.

Seventeen studies (13 KJD, 4 ISA) reporting on approximately 400 patients met the inclusion criteria. KJD yielded clinically important 1- to 2-year improvements in WOMAC/KOOS and VAS pain, with arthroplasty-free survival of roughly 75% to 85% at 5 to 9 years in selected series, accompanied by increases in radiographic joint-space width and MRI-derived cartilage thickness in the most affected compartment. ISA consistently improved WOMAC pain and function and showed higher 2-year arthroplasty-free survival than HTO or non-operative comparators.

Current evidence, based on small heterogeneous cohorts at low-to-moderate certainty, suggests that KJD and ISA can provide meaningful short- to mid-term symptom relief and delay arthroplasty in carefully selected patients. KJD and ISA address different indications and mechanisms and should be considered complementary rather than interchangeable joint-preserving strategies. Larger, independently replicated randomized trials with standardized structural and clinical endpoints are needed before widespread adoption.

This study investigated the effect of synovial cell fractionation on tenascin-C (TNC) expression in chondrocytes by coculturing human chondrocytes with synovial cells derived from osteoarthritis (OA) patients.

Human cartilage and synovium were isolated from patients undergoing total knee arthroplasty. Synovial cells were classified into CD68 positive- and negative groups using western blotting. Cocultures were performed for 7 days using Cell Culture Inserts. The expression of TNC, syndecan-4 (SDC4), and anabolic and catabolic factors was measured by real-time polymerase chain reaction. TNC levels in the medium were compared using enzyme-linked immunosorbent assay. Flow cytometry examined M1 and M2 macrophage proportions in synovial cells immediately after isolation, after 7 days of monoculture, and after coculture.

In the CD68 positive group, TNC and matrix metalloproteinase (MMP)-3 were significantly upregulated in cocultured chondrocytes, and SDC4 was significantly upregulated in cocultured synovial cells. TNC concentration in the medium was significantly higher in CD68 positive cocultures. M1 proportions were significantly higher in synovial cells immediately after isolation and in cocultured synovial cells than in those cultured alone.

Synovial cell fractionation differentially affects TNC and SDC4 expression. Macrophage-like synovial cells (MLS) increase TNC expression in chondrocytes and may contribute to OA pathology.

This study aimed to evaluate the clinical and biological outcomes of a one-step regenerative treatment using bone marrow aspirate concentrate (BMAC) on a hyaluronic acid scaffold combined with intraarticular platelet-rich plasma (PRP) for treatment of full-thickness cartilage lesions in the knee.

A total of 165 patients (mean age 26.4 years) with full thickness cartilage defects were included in the study. In a single-step procedure, bone marrow was aspirated from the iliac crest and centrifuged to obtain BMAC concentrate. PRP was prepared from whole blood. The BMAC concentrate was seeded onto a hyaluronic acid scaffold and implanted into the debrided cartilage defect and PRP was added intraarticularly. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and a semiquantitative grading scale (Excellent, Good, Fair) at one-year follow-up. All patients underwent MRI preoperatively and at one year follow-up, with cartilage repair evaluated using the MOCART-2.0 scoring system.

Significant improvements were observed in all KOOS subscales at one year. Semiquantitative grading revealed excellent outcomes in 50% of patients, good in 28%, and poor in 22%. MRI analysis showed an average MOCART-2.0 score of 71, with 36% of patients achieving excellent cartilage repair (MOCART 2.0 >80).

The combined use of BMAC on a hyaluronic acid scaffold and intraarticular PRP resulted in improved subjective clinical outcomes and demonstrated favourable biological cartilage healing responses at one year postoperatively. This one-step cartilage repair technique appears to be a clinically valid option for treatment of full-thickness cartilage lesions in the knee.

Return to work (RTW) is a key goal for patients treated for osteochondral lesions of the talus (OLT).

The primary objective of this review is to determine the RTW after surgical treatment of an OLT.

After preregistration, MEDLINE (PubMed), Embase and Cochrane Library were screened by two authors. RTW time and rate were extracted, and pooled if sufficient data was available. Two authors assessed methodological quality using the MINORS criteria.

A total of 18 studies were included for which 399 patients reported RTW rate and/or time. The overall methodological quality of the studies was poor. The RTW time ranged from 2 to 11 weeks post-operatively and varied across surgical techniques. The overall RTW rate was 93%, with arthroscopic procedures averaging 96%, and open procedures averaging 91% RTW.

After surgical treatment of OLTs, 93% of patients returned to work. Time to RTW ranged from 2 to 11 weeks, although reporting was heterogeneous and methodological quality was generally low. Future studies should include RTW as a core outcome and report work-related restrictions more consistently.

To describe recent trends in US MACI (autologous cultured chondrocytes on porcine collagen membrane) insurance approval rates, including the impact of defect location and the number of defects.

MyCartilageCare case management team provides insurance prior authorization support for potential MACI patients through Vericel Corporation, the manufacturer of MACI. Data from insurance claims from 2021 to 2022 were assessed for non-military patients aged 17 to 55 years. Insurance outcomes were summarized, with approval defined as pre-authorization or pre-determination for the MACI procedure being secured prior to the initiation of treatment or cases where an estimate of coverage was provided prior to the initiation of treatment, respectively.

A total of 5,158 cases were identified. In total, 87.7% of MACI cases were approved on initial submission, 9.4% were approved on appeal, 2.4% were not appealed, and 0.5% were denied after appeal. A total of 51.4% of cases included a patella defect, with similar rates of approval: 87.4% approved on initial submission, 9.6% approved on appeal, 2.5% not appealed, 0.5% denied after appeal. 29.9% contained more than one defect which were approved at similar rates: 87.1% approved on initial submission, 10.2% approved on appeal, 2.3% not appealed, and 0.5% denied after appeal.

MACI claims in the knee cartilage repair treatment algorithm are broadly supported by US third-party payers, with nearly 88% of all knee cartilage patients obtaining insurance approval on their initial submission and 97% of patients obtaining approval in total following appeal of initially denied claims. This is consistent across all groups including patella, non-patella, single, and multiple-defect cases.

To compare alignment parameters in bilateral lower extremities and evaluate the effect of contralateral limb on hip-knee-ankle angle (HKAA) longitudinally.

Native bilateral lower extremities of 3,045 Korean patients with long-leg radiographs were followed for progression of knee osteoarthritis. Concordance rates of Functional Knee Phenotypes (FKPs) and Coronal Plane Alignment of the Knee (CPAK), the proportion of patients with identical bilateral subtypes, were assessed. Varus, neutral, and valgus alignments were defined as baseline HKAA ≤177°, 177°< HKAA <183°, and HKAA ≥183°, respectively. Multivariable linear regressions for follow-up HKAA were conducted.

Concordance rates for FKPs and CPAK were 41.6% (95% confidence interval: 39.9-43.4%) and 53.5% (51.7-55.2%), respectively, at baseline and 35.5% (33.8-37.2%) and 55.4% (53.7-57.2%) at a mean 4.0-year follow-up. Contralateral parameters, Kellgren-Lawrence grade (P = 0.005) in bilateral varus group, medial proximal tibial angle (MPTA) (P = 0.046) in ipsilateral varus-contralateral neutral group, MPTA, and mechanical lateral distal femoral angle in bilateral neutral (P < 0.001; P = 0.012, respectively) and valgus (P = 0.003; P = 0.004) groups, were associated with follow-up HKAA. However, their standardized β values were smaller than ipsilateral values.

Concordance rates of FKPs and CPAK between bilateral limbs were 41.6% and 53.5% at baseline, respectively. Contralateral parameters have limited influence on coronal alignment progression compared with ipsilateral parameters.

To compare the dose-dependent chondrotoxicity of tranexamic acid (TXA) and aminocaproic acid (ACA) in vitro and in vivo.

In vitro, human chondrocytes were exposed to TXA or ACA (0-50 mg/ml), and cytotoxicity was assessed. In vivo, a rat model of monoiodoacetate-induced osteoarthritis was used to evaluate cartilage damage following intra-articular injections of TXA or ACA.

In vitro, both TXA and ACA reduced chondrocyte viability in a dose-dependent manner, with significant cytotoxicity observed at concentrations ≥20 mg/ml. TXA was more toxic than ACA at these higher concentrations. Apoptosis increased markedly at 30 mg/ml for both agents. In the rat osteoarthritis model, joints treated with TXA or ACA showed greater cartilage erosion and matrix loss compared to controls, with TXA causing more severe damage.

Both TXA and ACA are chondrotoxic in a dose-dependent manner, with TXA demonstrating greater potency. Lower concentrations (≤10 mg/ml) are recommended for topical use in cartilage-preserving surgery to minimize potential damage.

This review aims to elucidate the mechanisms underlying chondrocyte senescence in osteoarthritis (OA) from 4 core perspectives: extracellular inflammation, mechanical overload and stress, intracellular metabolic and signaling dysregulation, and genetics-related alterations. It further summarizes emerging therapeutic strategies targeting chondrocyte senescence to address the unmet clinical need for disease-modifying OA interventions.

Accumulating evidence indicates that chondrocyte senescence drives OA progression through multiple interconnected mechanisms. These include amplification of inflammation and extracellular matrix degradation via the senescence-associated secretory phenotype (SASP), disruption of anabolic-catabolic homeostasis, dysregulation of mechanotransduction pathways under excessive mechanical load, and reshaping of intracellular metabolism and redox balance. Additional contributing mechanisms involve epigenetic dysregulation, non-coding RNA–mediated gene modulation, and impaired autophagy. Therapeutic approaches under preclinical or clinical investigation encompass senolytic and senomorphic agents, chondroprotective biological materials, genetic or RNA-based interventions, as well as strategies targeting SASP modulation and extracellular microenvironment repair.

Chondrocyte senescence serves as a central convergent mechanism in OA pathogenesis and a promising target for disease-modifying therapies. Advances in mechanistic understanding and senescence-targeted interventions offer new avenues for translational innovation, though critical challenges related to specificity, safety, and long-term efficacy require further resolution.

People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often go on to develop post-traumatic osteoarthritis (PTOA). ACL injuries are often treated with ACL reconstruction, but there is typically a gap of several weeks between injury and surgery. However, it is unclear how loading or unloading of the injured joint during the early postinjury period affects the progression of PTOA. The goal of this study was to determine how unloading between noninvasive ACL injury and surgical restabilization of the injured joint affects PTOA progression in mice.

Mice were subjected to noninvasive ACL injury or no injury followed by 1 week of hindlimb unloading (HLU) or normal cage activity. After 1 week of HLU or cage activity, mice underwent restabilization surgery or no surgery. ACL injury resulted in considerable epiphyseal trabecular bone loss regardless of HLU or cage activity. HLU groups exhibited significantly reduced chondrophyte/osteophyte formation, OA scoring, and synovitis at day 42. Single-cell RNA sequencing revealed that 1 week of HLU resulted in more neutrophils and less monocytes-macrophages in the injured joint.

This study establishes that 1 week of HLU after ACL injury effectively slowed PTOA progression, suggesting that the early inflammatory response and joint instability play a key role in PTOA initiation and progression, and neutrophils and monocytes-macrophages play roles in the modulation. However, subsequent joint restabilization surgery caused greater inflammatory protease activity in the joint and exacerbated the loss of epiphyseal trabecular bone but did not significantly diminish OA score or synovitis.

This study investigated whether hyperbaric oxygen (HBO) therapy, initiated after disease establishment, exerts disease-modifying effects in a rat model of anterior cruciate ligament transection (ACLT)-induced post-traumatic osteoarthritis (PTOA).

Thirty-six Sprague-Dawley rats underwent ACLT surgery. HBO therapy commenced at Week 11 (established OA phase) and continued for 6 weeks. Outcomes were assessed using Von Frey testing, multimodal 7T MRI (T2* quantification and pharmacokinetic DCE-MRI), and histopathology.

By Week 10, ACLT induced significant mechanical allodynia, T2* prolongation, and SCB perfusion abnormalities (A increase; k _ep , k _el decrease). Following HBO intervention, the ACLT+HBO group exhibited a marked recovery in mechanical withdrawal threshold and significantly lower T2* values compared to the ACLT-only group (p < 0.01). DCE-MRI demonstrated that HBO restored clearance kinetics (k _el , k _ep ) and suppressed pathological blood volume (A), effectively remediating subchondral venous congestion. Histologically, HBO reduced OARSI scores and suppressed α-SMA-positive vascular invasion across the tidemark. These findings suggest that HBO therapy may alleviate PTOA by suppressing catabolic activity and normalizing pathological subchondral angiogenesis.

HBO therapy, initiated post-pathogenesis, effectively attenuates nociception and preserves cartilage integrity by restoring subchondral microcirculatory homeostasis. These findings establish HBO as a potent, non-invasive disease-modifying strategy for PTOA.

Osteoarthritis (OA) is more common in women, suggesting a link to estrogen. Estrogen supports cartilage homeostasis and metabolism via two receptors: ERα and ERβ. Mechanical stress is the primary cause of OA and affects cellular functions, including receptor activity. The link between excessive mechanical stress and ERs in cartilage is poorly understood. This study examined ER expression changes in chondrocytes under mechanical stress and the role of estrogen in cartilage degradation and ER regulation.

ATDC5 chondrocytes were treated with 17β-estradiol (E2; 1.0 × 10⁻⁷M) and subjected to cyclic tensile strain using the Flexcell Tension Plus FX-2000. Total RNA and proteins were extracted, and IL-1β and MMP-13 expression were analyzed using RT-PCR and western blotting. RT-PCR was used to examine the expression of ERα and ERβ.

The CTS group had significantly downregulated ERα expression at all time points and upregulated ERβ expression after 3 and 6 hours compared with controls. In the E2+CTS group, IL-1β and MMP-13 expression were suppressed after 3 and 6 hours, coinciding with significant upregulation of ERβ compared with the CTS group.

Estrogen exerts a chondroprotective effect under excessive mechanical stress, suggesting that ERβ mediates this effect.

Viscosupplementation (VS) by intra-articular injections of hyaluronic acid (HA) is an increasingly used treatment of hip osteoarthritis (OA). However, there are no clear European recommendations for its use.

Twelve members of the European Viscosupplementation Consensus Group (EUROVISCO), made up of rheumatologists, orthopedic surgeons, and rehabilitation physicians from European countries, were asked to make a therapeutic decision on 23 statements based on an exhaustive analysis of the literature and their clinical experience, using the Delphi method. For each statement, the strength of agreement and the level of consensus were calculated by the chairman of the group

The expert panel reached unanimous or high consensus, either for or against, on 16 of the proposed statements. The main ones are: Current evidence and the results of observational trials support the use of VS in patients with hip OA who do not require surgery. VS is more effective in cases of mild to moderate hip OA. Hip VS is safe and well tolerated, even with repeated injections. The outcome of VS depends on the viscosupplement used. A standard X-ray must be obtained before deciding on VS. VS must be performed under imaging guidance. A single injection regimen is preferable to repeat injections. VS can be considered for individuals who wish to postpone surgery. Hip replacement surgery should not be performed within 3 months of VS. VS should not be used to treat an osteoarthritis flare. VS is part of a multimodal treatment for hip OA.

This set of recommendations is intended to help practitioners make decisions about HA VS in patients with OA.

To evaluate the serial changes in graft diameter during the 2 years following anterior cruciate ligament (ACL) reconstruction using serial magnetic resonance imaging (MRI).

This study involved 38 patients (38 knees) who underwent arthroscopic ACL reconstruction and had MRI immediately after surgery, at 1 year, and at 2 years. Graft diameter was measured at the distal, middle, and proximal levels of the intra-articular length, selecting the sagittal MRI slice that optimally showed the graft at each level. Correlation analysis was performed to identify the relationship between the difference of each graft diameter and demographic data and postoperative assessment results.

Post hoc analysis over time showed substantial thickening from the immediate postoperative to the 1-year scan (distal, +3.098 mm; middle, +3.284 mm; proximal, +3.074 mm; all P < 0.001), a modest but significant reduction from 1 to 2 years (distal, −0.749 mm; middle, −0.699 mm; proximal, −0.574 mm; all P < 0.001), and persistent enlargement at 2 years compared with those at baseline (distal, +2.348 mm; middle, +2.586 mm; proximal, +2.499 mm; all P < 0.001). Regarding the correlation analyses, the graft diameter measurements at the proximal, middle, and distal sites across the 3 different time points were not significantly correlated with the postoperative results.

The graft diameter demonstrated a unimodal peak at 1 year postoperatively, followed by a gradual decrease until 2 years; however, it remained thicker at 2 years than immediately after surgery. These changes were not correlated with postoperative patients’ reported outcomes and stability.

To investigate water and lipid composition changes in knee subchondral bone marrow and cartilage in chronic kidney disease (CKD) patients compared with age- and sex-matched healthy controls using magnetic resonance spectroscopy (MRS) and T2 mapping.

This IRB-approved case-control study included 20 CKD patients (12 men, 8 women) and 20 age- and sex-matched healthy controls (10 men, 10 women). MRS and T2 measurements were performed on regions of interest in the knee subchondral bone and cartilage. Water content, lipid composition, fat content, and the unsaturation index (UI) were quantified using LCModel. Differences between groups were assessed using independent samples T-tests.

The CKD group showed a significantly higher lipid UI compared with controls (P = 0.035). In subgroup analysis, women with CKD had significantly higher water content (4.7 ppm), lower fat content, and higher lipid UI than female controls (P = 0.023, 0.048, and 0.018, respectively). No significant differences were observed between men with CKD and male controls (all P > 0.4). Among CKD patients, men had significantly lower lipid composition (5.3 ppm) and lipid UI compared with women (P = 0.026 and 0.012, respectively). T2 values were significantly elevated in CKD patients (P = 0.016 for men; P = 0.031 for women).

Quantitative MRS and T2 mapping are feasible tools for assessing CKD-related changes in the knee joint. Increased unsaturated lipid content and water in subchondral bone may contribute to early degenerative changes.

To determine the influence of Spirulina supplementation on the response of bovine chondrocytes to mechanical compression with respect to extracellular matrix dynamics (proteoglycan and collagen) and inflammation [nitric oxide (NO)].

Bovine chondrocytes were embedded in agarose constructs and cultured for 14 days in basal media or media supplemented with Spirulina (30 or 90 µg/mL). Constructs were exposed to 10% dynamic compression. DNA content, NO levels, proteoglycan content and release, and collagen synthesis were measured to assess extracellular matrix (ECM) responses.

DNA content did not differ among groups. Spirulina supplementation increased NO levels in constructs and media, with the highest effect observed at 90 µg/mL. Proteoglycan content decreased in Spirulina-treated constructs and declined further after compression, while proteoglycan release increased across all groups. Collagen synthesis and content were elevated by Spirulina, particularly at 90 µg/mL, and further increased following dynamic compression.

Spirulina supplementation, particularly at higher concentrations, enhances ECM turnover and increases NO production in chondrocytes under mechanical loading, indicating potential modulation of matrix dynamics that may be beneficial. However, these results are derived from an in vitro model and may not fully represent in vivo physiological conditions.

Osteoarthritis (OA) is characterized by progressive cartilage degeneration driven by inflammation-induced chondrocyte injury, while effective disease-modifying therapies are still lacking. Exosome-based cell-free approaches are emerging as promising alternatives, but their key molecular mediators remain incompletely defined.

Adipose-derived stem cells (ADSCs) were pretreated with platelet-rich plasma (PRP) to enhance exosomal function. Isolated exosomes were characterized, and LINC01106 expression was modulated by overexpression or knockdown. Interleukin (IL)-1β-stimulated chondrocytes were used to assess apoptosis, inflammatory cytokine secretion, oxidative stress, and extracellular matrix degradation. The LINC01106/miR-34a-5p/SIRT1 axis was examined using luciferase reporter assays, quantitative real-time polymerase chain reaction (PCR), Western blotting, and immunofluorescence.

PRP pretreatment markedly increased LINC01106 enrichment in ADSC-derived exosomes. LINC01106-rich exosomes significantly reduced chondrocyte apoptosis, suppressed tumor necrosis factor-α (TNF-α) and IL-6 secretion, alleviated oxidative stress, and attenuated matrix metalloproteinase (MMP)-mediated matrix degradation under IL-1β stimulation. Mechanistically, LINC01106 acted as a competing endogenous RNA that sequestered miR-34a-5p, thereby restoring SIRT1 expression. Rescue experiments demonstrated that miR-34a-5p overexpression or SIRT1 silencing abolished these protective effects. In addition, LINC01106-enriched exosomes inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway activation in a SIRT1-dependent manner.

PRP-stimulated ADSC-derived exosomes confer potent chondroprotective effects through the LINC01106/miR-34a-5p/SIRT1 pathway, highlighting a promising cell-free therapeutic strategy for OA.