A multifunctional nanogel encapsulating layered double hydroxide for enhanced osteoarthritis treatment via protection of chondrocytes and ECM.

Osteoarthritis (OA) is characterized by progressive and irreversible damage to the articular cartilage and a consecutive inflammatory response. However, the majority of clinical drugs for OA treatment only alleviate symptoms without addressing the fundamental pathology. To mitigate this issue, we developed an inflammation-responsive carrier and encapsulated bioactive material, namely, LDH@TAGel. The LDH@TAGel was designed with anti-inflammatory and antioxidative abilities, aiming to directly address the pathology of cartilage damage. In particular, LDH was confirmed to restore the ECM secretion function of damaged chondrocytes and attenuate the expression of catabolic matrix metalloproteinases (Mmps). While TAGel showed antioxidant properties by scavenging ROS directly. In vitro evaluation revealed that the LDH@TAGel could protect chondrocytes from inflammation-induced oxidative stress and apoptosis via the Nrf2/Keap1 system and Pi3k-Akt pathway. In vivo experiments demonstrated that the LDH@TAGel could alleviated the degeneration and degradation of cartilage induced by anterior cruciate ligament transection (ACLT). The OARSI scores indicating OA severity decreased significantly after three weeks of intervention. Moreover, the IVIS image revealed that LDH@TAGel enhances the controlled release of LDH in a manner that can be customized according to the severity of OA, allowing adaptive, precise treatment. In summary, this novel design effectively alleviates the underlying pathological causes of OA-related cartilage damage and has emerged as a promising biomaterial for adaptive, cause-targeted OA therapies.

The Role of Neuromodulation and Potential Mechanism in Regulating Heterotopic Ossification.

Heterotopic ossification (HO) is a pathological process characterized by the aberrant formation of bone in muscles and soft tissues. It is commonly triggered by traumatic brain injury, spinal cord injury, and burns. Despite a wide range of evidence underscoring the significance of neurogenic signals in proper bone remodeling, a clear understanding of HO induced by nerve injury remains rudimentary. Recent studies suggest that injury to the nervous system can activate various signaling pathways, such as TGF-ß, leading to neurogenic HO through the release of neurotrophins. These pathophysiological changes lay a robust groundwork for the prevention and treatment of HO. In this review, we collected evidence to elucidate the mechanisms underlying the pathogenesis of HO related to nerve injury, aiming to enhance our understanding of how neurological repair processes can culminate in HO.

A systematic review and meta-analysis of Internet-based self-help interventions for mental health among adolescents and college students.

Purpose: This meta-analysis aims to evaluate the impact of Internet-based self-help interventions on the mental health of adolescents and college students. Methods: We conducted a systematic review of randomized controlled trials (RCTs) that investigated Internet-based self-help interventions aiming to mitigate mental health symptoms such as anxiety and depression, as well as managing high levels of stress, among adolescents and college students. Our search spanned databases including Web of Science, PubMed, Cochrane Library, and Embase, up until November 1st, 2022. It is essential to emphasize that our focus was the evaluation of symptoms (continuous outcomes), rather than the diagnosis of specific mental disorders. The meta-analysis was performed using the R version 4.3.1. The effect size measure was the standardized mean difference (SMD), and random-effects models were used to pool data from eligible RCTs. Subgroup analyses were carried out to examine variations in intervention effects based on factors such as sample type, intervention modality, guidance type, and intervention duration. Results: The meta-analysis was based on 25 comparisons involving a total of 4480 participants. In comparison to the control group (n = 2125), participants receiving interventions (n = 2355) reported significant reductions in symptoms of anxiety, depression, and stress, along with a significant improvement in quality of life. Specifically, for depression, we observed moderate intervention effects (SMD = -0.42, 95 % CI: -0.56, -0.27), and a similar pattern was seen for quality of life (SMD = 0.36, 95%CI: 0.22, 0.49). Small intervention effects were found for anxiety (SMD = -0.35, 95 % CI [-0.48, -0.22]) and stress (SMD = -0.35, 95 % CI [-0.51, -0.20]). Given significant heterogeneity, subgroup analyses were conducted for anxiety and depression, considering factors such as sample type, intervention method, and intervention duration. Notably, college students experienced more significant benefits in both anxiety and depression alleviation compared to adolescents. Longer interventions (>8 weeks) were particularly effective in reducing anxiety and depression. Additionally, third-wave cognitive-behavioral therapy (CBT) showed pronounced intervention effects in both outcome measures, while the presence of guidance did not notably influence results. Conclusion: This meta-analysis underscores the positive impact of Internet-based self-help programs in alleviating the symptoms of psychological disorders among adolescents and college students. However, it is crucial to acknowledge that the available evidence exhibits inconsistencies and limitations. Therefore, further research utilizing rigorous methodologies is necessary to verify and broaden the findings of this meta-analysis.

Correction: Indocyanine-green-loaded microbubbles for localization of sentinel lymph node using near-infrared fluorescence/ultrasound imaging: a feasibility study.

[This corrects the article DOI: 10.1039/C5RA26814A.].

HYBID in osteoarthritis: Potential target for disease progression.

HYBID is a new hyaluronan-degrading enzyme and exists in various cells of the human body. Recently, HYBID was found to over-express in the osteoarthritic chondrocytes and fibroblast-like synoviocytes. According to these researches, high level of HYBID is significantly correlated with cartilage degeneration in joints and hyaluronic acid degradation in synovial fluid. In addition, HYBID can affect inflammatory cytokine secretion, cartilage and synovium fibrosis, synovial hyperplasia via multiple signaling pathways, thereby exacerbating osteoarthritis. Based on the existing research of HYBID in osteoarthritis, HYBID can break the metabolic balance of HA in joints through the degradation ability independent of HYALs/CD44 system and furthermore affect cartilage structure and mechanotransduction of chondrocytes. In particular, in addition to HYBID itself being able to trigger some signaling pathways, we believe that low-molecular-weight hyaluronan produced by excess degradation can also stimulate some disease-promoting signaling pathways by replacing high-molecular-weight hyaluronan in joints. The specific role of HYBID in osteoarthritis is gradually revealed, and the discovery of HYBID raises the new way to treat osteoarthritis. In this review, the expression and basic functions of HYBID in joints were summarized, and reveal potential role of HYBID as a key target in treatment for osteoarthritis.

Psychological intervention for negative emotions aroused by COVID-19 pandemic in university students: A systematic review and meta-analysis.

The COVID-19 pandemic has been suggested to cause psychological problems such as anxiety, depression, panic, and insomnia. This systematic review and meta-analysis aims to assess the efficacy of psychological interventions (including CBT, DBT, and mindfulness based interventions) in reducing distressing feelings in college students during the COVID-19 pandemic. Randomized controlled trials (RCTs) on psychological interventions for reducing negative emotions among college students during the COVID-19 epidemic were searched in databases Web of Science, PubMed, Cochrane Library, Embase, Scopus, PsychInfo, CNKI, WanFang, and VIP. We utilized Cochrane risk of bias assessment technique to assess the quality of included RCTs. The data were analyzed using RevMan 5.4. Eight RCTs were finally included involving 1,496 participants. According to the meta-analysis results, psychotherapies could significantly alleviate anxiety, depression, and stress symptoms among university students, [MD = -0.98, 95%CI (-1.53, -0.43), p<0.001] [SMD = -0.47, 95%CI (-0.77, -0.16), p = 0.003] [MD = -1.53, 95%CI (-2.23, -0.83), p <0.001]. The difference in attenuation of somatization symptoms between the two groups was not statistically significant [SMD = -0.42, 95%CI (-1.41, 0.56), p = 0.40]. Psychotherapy might effectively alleviate anxiety, depression, and stress in university students caused by the COVID-19 pandemic. It could be considered the preferred strategy for reducing negative emotions and improving the quality of life of university students.

Connexin43 in Musculoskeletal System: New Targets for Development and Disease Progression.

Connexin43, which is the most highly expressed connexin subtype in the musculoskeletal system, exists in a variety of bone cells, synovial tissue, and cartilage tissue. Connexin43 has been suggested to be a key regulator of bone homeostasis. Studies have shown aberrant Connexin43 expression in musculoskeletal disorders, such as osteoporosis, osteoarthritis, and rheumatoid arthritis. During cellular activities, Connexin43 can participate in the formation of functionally specific gap junctions and hemichannels and can exert independent cellular regulatory and signaling functions through special C-termini. The critical role of Connexin43 in physiological development and disease progression has been gradually revealed. In this article, the function of Connexin43 in musculoskeletal tissues is summarized, revealing the potential role of Connexin43 as a key target in the treatment of related bone and muscle disorders and the need for further discovery.

Roles of the calcified cartilage layer and its tissue engineering reconstruction in osteoarthritis treatment.

Sandwiched between articular cartilage and subchondral bone, the calcified cartilage layer (CCL) takes on both biomechanical and biochemical functions in joint development and ordinary activities. The formation of CCL is not only unique in articular cartilage but can also be found in the chondro-osseous junction adjacent to the growth plate during adolescence. The formation of CCL is an active process under both cellular regulation and intercellular communication. Abnormal alterations of CCL can be indications of degenerative diseases including osteoarthritis. Owing to the limited self-repair capability of articular cartilage and core status of CCL in microenvironment maintenance, tissue engineering reconstruction of CCL in damaged cartilage can be of great significance. This review focuses on possible tissue engineering reconstruction methods targeting CCL for further OA treatment.

Exosomes in osteoarthritis: Updated insights on pathogenesis, diagnosis, and treatment.

Osteoarthritis (OA) has remained a prevalent public health problem worldwide over the past decades. OA is a global challenge because its specific pathogenesis is unclear, and no effective disease-modifying drugs are currently available. Exosomes are small and single-membrane vesicles secreted via the formation of endocytic vesicles and multivesicular bodies (MVBs), which are eventually released when MVBs fuse with the plasma membrane. Exosomes contain various integral surface proteins derived from cells, intercellular proteins, DNAs, RNAs, amino acids, and metabolites. By transferring complex constituents and promoting macrophages to generate chemokines and proinflammatory cytokines, exosomes function in pathophysiological processes in OA, including local inflammation, cartilage calcification and degradation of osteoarthritic joints. Exosomes are also detected in synovial fluid and plasma, and their levels continuously change with OA progression. Thus, exosomes, specifically exosomal miRNAs and lncRNAs, potentially represent multicomponent diagnostic biomarkers for OA. Exosomes derived from various types of mesenchymal stem cells and other cell or tissue types affect angiogenesis, inflammation, and bone remodeling. These exosomes exhibit promising capabilities to restore OA cartilage, attenuate inflammation, and balance cartilage matrix formation and degradation, thus demonstrating therapeutic potential in OA. In combination with biocompatible and highly adhesive materials, such as hydrogels and cryogels, exosomes may facilitate cartilage tissue engineering therapies for OA. Based on numerous recent studies, we summarized the latent mechanisms and clinical value of exosomes in OA in this review.

Inhibition of Integrin αvß6 Activation of TGF-ß Attenuates Tendinopathy.

Tendinopathy is a common tendon disorder that causes pain and impairs function. It is the most common reason for consultation with musculoskeletal specialists. The available therapies for tendinopathy are limited in number and efficacy and have unclear cellular and molecular mechanisms. Here it is shown that transforming growth factor-beta (TGF-ß) activated by integrin αvß6 promotes tendinopathy in mice. Excessive active TGF-ß is found during tendinopathy progression, which led to tenocytes' phenotype transition to chondrocytes. Transgenic expression of active TGF-ß in tendons induced spontaneous tendinopathy, whereas systemic injection of a TGF-ß neutralizing antibody attenuated tendinopathy. Inducible knockout of the TGF-ß type 2 receptor gene (Tgfbr2) in tenocytes inhibited tendinopathy progression in mice. Moreover, it is found that integrin αvß6 induces TGF-ß activation in response to mechanical load in tendons. Conditional knockout of the integrin αv gene in tendons prevented tendinopathy in mice. The study suggests that integrin αvß6 activation of TGF-ß is the mechanism of tendinopathy, and that integrin αvß6 may be a therapeutic target in tendinopathy.

Chondrogenesis mediates progression of ankylosing spondylitis through heterotopic ossification.

Ankylosing spondylitis (AS) is chronic inflammatory arthritis with a progressive fusion of axial joints. Anti-inflammatory treatments such as anti-TNF-α antibody therapy suppress inflammation but do not effectively halt the progression of spine fusion in AS patients. Here we report that the autoimmune inflammation of AS generates a microenvironment that promotes chondrogenesis in spine ligaments as the process of spine fusion. Chondrocyte differentiation was observed in the ligaments of patients with early-stage AS, and cartilage formation was followed by calcification. Moreover, a large number of giant osteoclasts were found in the inflammatory environment of ligaments and on bony surfaces of calcified cartilage. Resorption activity by these giant osteoclasts generated marrow with high levels of active TGF-ß, which induced new bone formation in the ligaments. Notably, no Osterix+ osteoprogenitors were found in osteoclast resorption areas, indicating uncoupled bone resorption and formation. Even at the late and maturation stages, the uncoupled osteoclast resorption in bony interspinous ligament activates TGF-ß to induce the progression of ossification in AS patients. Osteoclast resorption of calcified cartilage-initiated ossification in the progression of AS is a similar pathologic process of acquired heterotopic ossification (HO). Our finding of cartilage formation in the ligaments of AS patients revealed that the pathogenesis of spinal fusion is a process of HO and explained why anti-inflammatory treatments do not slow ankylosing once there is new bone formation in spinal soft tissues. Thus, inhibition of HO formation, such as osteoclast activity, cartilage formation, or TGF-ß activity could be a potential therapy for AS.

Targeted Delivery of Curcumin to Polyethylene-Induced Osteolysis by Magnetically Guided Zoledronate-Anchored Poly Lactic-Co-Glycolic Acid Nanoparticles via Repressing NF-κB Signaling.

Aseptic loosening induced by periprosthetic osteolysis (PPO) is the leading complication of total joint arthroplasty (TJA) and results in patients having to receive revision surgery. However, there is still no efficient drug to prevent or even slow the pathological process. Herein, we report novel dual-targeted, curcumin-loaded Poly lactic-co-glycolic acid nanoparticles (ZSCNPs) to inhibit polyethylene-induced osteolysis. These ZSCNPs have good biocompatibility and excellent bone binding affinity. Under external magnetic field guidance, the ZSCNPs can specifically target osteolytic sites with sustained curcumin release, efficiently suppress the effect of IκB kinase, subsequently inhibit activation of the nuclear factor-kappa B (NF-κB) signaling pathway, and ultimately prevent osteoclast formation and particle-induced osteolysis. Therefore, these novel dual-targeted, drug-loaded nanoparticles could be applied as a useful strategy for targeted treatment of PPO after TJA.

Pyroptosis Plays a Role in Osteoarthritis.

Recent studies have revealed novel forms of cell death beyond the canonical types of cellular apoptosis and necrosis, and these novel forms of cell death are induced by extreme microenvironmental factors. Pyroptosis, a type of regulated cell death, occurs when pattern recognition receptors (PRRs) induce the activation of cysteine-aspartic protease 1 (caspase-1) or caspase-11, which can trigger the release of the pyrogenic cytokines interleukin-1ß (IL-1ß) and IL-18. Osteoarthritis (OA), the most common joint disease worldwide, is characterized by low-grade inflammation and increased levels of cytokines, including IL-1ß and IL-18. Additionally, some damaged chondrocytes associated with OA exhibit morphological changes consistent with pyroptosis, suggesting that this form of regulated cell death may contribute significantly to the pathology of OA. This review summarizes the molecular mechanisms of pyroptosis and shows the critical role of NLRP3 (NLR family, pyrin domain containing 3; NLR refers to "nucleotide-binding domain, leucine-rich repeat") inflammasomes. We also provide evidence describing potential role of pyroptosis in OA, including the relationship with OA risk factors and the contribution to cartilage degradation, synovitis and OA pain.

Extracorporeal shockwave treatment in knee osteoarthritis: therapeutic effects and possible mechanism.

Osteoarthritis (OA), the most common degenerative joint disease, is characterized by the cardinal symptoms of chronic pain and restricted joint activity. The complicated pathological changes associated with OA and unclear mechanistic etiology have rendered existing non-surgical OA management options unsatisfactory. Increasing clinical and experimental evidence suggests that extracorporeal shockwave therapy (ESWT) is beneficial in OA treatment. ESWT is found to have modifying effects on cartilage and subchondral bone alterations in OA progression, as well as the clinical complaints of patients, including chronic pain and limited joint activities. However, the specific treatment strategy regarding the dosage and frequency of ESWT is still underdetermined. This review discusses the existing evidence regarding the therapeutic indications and possible mechanism of ESWT for OA treatment.

Aberrant subchondral osteoblastic metabolism modifies NaV1.8 for osteoarthritis.

Pain is the most prominent symptom of osteoarthritis (OA) progression. However, the relationship between pain and OA progression remains largely unknown. Here we report osteoblast secret prostaglandin E2 (PGE2) during aberrant subchondral bone remodeling induces pain and OA progression in mice. Specific deletion of the major PGE2 producing enzyme cyclooxygenase 2 (COX2) in osteoblasts or PGE2 receptor EP4 in peripheral nerve markedly ameliorates OA symptoms. Mechanistically, PGE2 sensitizes dorsal root ganglia (DRG) neurons by modifying the voltage-gated sodium channel NaV1.8, evidenced by that genetically or pharmacologically inhibiting NaV1.8 in DRG neurons can substantially attenuate OA. Moreover, drugs targeting aberrant subchondral bone remodeling also attenuates OA through rebalancing PGE2 production and NaV1.8 modification. Thus, aberrant subchondral remodeling induced NaV1.8 neuronal modification is an important player in OA and is a potential therapeutic target in multiple skeletal degenerative diseases.

Many people will suffer from joint pain as they age, particularly in their knees. The most common cause of this pain is osteoarthritis, a disease that affects a tissue inside joints called cartilage. In a healthy knee, cartilage acts as a shock absorber. It cushions the ends of bones and enables them to move smoothly against one another. But in osteoarthritis, cartilage gradually wears away. As a result, the bones within a joint rub against each other whenever a person moves. This makes activities such as running or climbing stairs painful. But how does this pain arise? Previous work has implicated cells called osteoblasts. Osteoblasts are found in the area of the bone just below the cartilage. They produce new bone tissue throughout our lives, enabling our bones to regenerate and repair. Each time we move, forces acting on the knee joint activate osteoblasts. The cells respond by releasing a key molecule called PGE2, which is a factor in pain pathways. The joints of people with osteoarthritis produce too much PGE2. But exactly how this leads to increased pain sensation has been unclear. Zhu et al. now complete this story by working out how PGE2 triggers pain. Experiments in mice reveal that PGE2 irritates the nerve fibers that carry pain signals from the knee joint to the brain. It does this by activating a channel protein called Na_v1.8, which allows sodium ions through the membranes of those nerve fibers. Zhu et al. show that, in a mouse model of osteoarthritis, Na_v1.8 opens too widely in response to binding of PGE2, so the nerve cells become overactive and transmit a stronger pain sensation. This means that even small movements cause intense pain signals to travel from the joints to the brain. Building on their findings, Zhu et al. developed a drug that acts directly on bone to reduce PGE2 production, and show that this drug reduces pain in mice with osteoarthritis. At present, there are no treatments that reverse the damage that occurs during osteoarthritis, but further testing will determine whether this new drug could one day relieve joint pain in patients.

Degradation and osteogenic induction of a SrHPO4-coated Mg-Nd-Zn-Zr alloy intramedullary nail in a rat femoral shaft fracture model.

Magnesium and Mg-based alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. However, the drawbacks of these materials include high hydrogen gas production, unexpected corrosion resistance, and insufficient mechanical strength duration. Surface modification can protect these biomaterials and induce osteogenesis. In this work, a SrHPO4 coating was developed for our patented biodegradable Mg-Nd-Zn-Zr alloy (abbr. JDBM) through a chemical deposition method. The coating was characterized by in vitro immersion, ion release, and cytotoxicity tests, which showed a slower corrosion behavior and excellent cell viability. RNA sequencing of MC3T3E1 cells treated with SrHPO4-coated JDBM ion release test extract showed increased Tlr4, followed by the activation of the downstream PI3K/Akt signaling pathway, causing proliferation and growth of pre-osteoblasts. An intramedullary nail (IMN) was implanted in a femoral fracture rat model. Mechanical test, radiological and histological analysis suggested that SrHPO4-coated JDBM has superior mechanical properties, induces more bone formation, and decreases the degradation rate compared with uncoated JDBM and the administration of TLR4 inhibitor attenuated the new bone formation for fracture healing. SrHPO4 is a promising coating for JDBM implants, particularly for long-bone fractures.

A Comparative Study of Patients' Subjective Feelings Toward Total Hip Arthroplasty with Patient-Specific Instruments and Traditional Total Hip Arthroplasty.

OBJECTIVE: To determine whether differences exist in patients' subjective feelings, daily life, and surgical satisfaction between those who underwent surgery for developmental dysplasia of the hip (DDH) using patient-specific instruments (PSIs) and those who underwent traditional surgical total hip arthroplasty (THA). METHODS: We selected 30 adult patients with various types of DDH who underwent surgery during 2016-2017 at our hospital. The patients were divided into PSI surgery group and the traditional surgery group. All patients underwent follow-up, and we collected data on the Harris Hip Score, Oxford University Hip Score (OHS), Forgotten Joint Score (FJS-12), Visual Analogue Scale (VAS) score, patient satisfaction score, intraoperative surgical time, amount of bleeding and postoperative complications incidence for both groups. We then performed statistical analyses on the data. RESULTS: The Harris Hip Score, OHS, VAS score, patient satisfaction score, and mean bleeding volume did not differ statistically significantly (t-tests, P > 0.05). No statistically significant differences were found between surgical groups in the incidence of complication and sub-trochanteric osteotomy, or in the surgical side (chi-square tests, P > 0.05). For the experimental group, the FJS-12 score was 80.0 ± 12.0, and for the control group the score was 68.5 ± 16.1. The operative time of the experimental group was 138.4 ± 32.2 min, while that of the control group was 88.9 ± 26.8 min. The values of these data differed significantly (t-tests, P < 0.05). CONCLUSIONS: The novel PSI designed by our group has certain advantages for the short-term subjective feelings of patients after THA, but it may cause prolonged operative times.

[Mid- and long-term effectiveness of total hip arthroplasty with Ribbed femoral stem prosthesis in 354 cases].

OBJECTIVE: To evaluate the mid- and long-term effectiveness of total hip arthroplasty (THA) with Ribbed femoral stem prosthesis. METHODS: A clinical data of 354 patients (384 hips) with hip disease who underwent THA with Ribbed femoral stem prostheses between October 2006 and May 2016 was retrospectively analyzed. There were 171 males and 183 females, with an average age of 53.4 years (range, 20-82 years). There were 324 cases of single hip and 30 cases of bilateral hips. The cause of THA included the avascular necrosis of the femoral head in 151 cases (159 hips), hip osteoarthritis in 134 cases (136 hips), rheumatoid arthritis in 43 cases (43 hips), ankylosing spondylitis in 20 cases (40 hips), and trauma in 6 cases (6 hips). The Harris score of total 354 patients before operation was 42.34±8.89. Harris scores were used to evaluate hip function after operation. X-ray films were used to determine the length of the lower limb, the radiolucent line on the femur side, the stability of the prosthesis, and the occurrence of stress shielding. RESULTS: The incisions healed by first intention. All patients were followed up 2-11 years with an average of 7.4 years. The Harris score at last follow-up was 80.52±7.61, which significantly increased when compared with preoperative score ( t=134.804, P=0.000). Two cases (2 hips) of prosthetic infections, 3 cases (3 hips) of prothesis loosening, and 4 cases (4 hips) of periprosthetic fractures, and 48 cases (48 hips) of mild to moderate thigh pain occurred after operation. X-ray films showed 76 cases (78 hips) with radiolucent lines on the femur side and stress shielding. According to the Engh's method, there were 364 hips of bone ingrowth, 15 hips of fibrosis ingrowth, and 5 hips of prosthesis instability. The femoral stem subsidence occurred in 25 cases (25 hips), and the difference in leg length discrepancy was more than 10 mm in 5 patients. CONCLUSION: THA with Ribbed femoral stem prosthesis can achieve satisfactory effectiveness with good initial stability and rapid bone growth. The incidence of stress shielding is relatively high, but the stress shielding has no significant impact on the mid- and long-term survival rate and effectiveness of femoral prosthesis.

Protection Effect of Curcumin for Macrophage-Involved Polyethylene Wear Particle-Induced Inflammatory Osteolysis by Increasing the Cholesterol Efflux.

BACKGROUND Periprosthetic osteolysis, induced by wear particles and inflammation, is a common reason for failure of primary arthroplasty. Curcumin, a nature phenol from plants, has been reported to reduce the inflammation in macrophages. This study aimed to investigate the potential effect of curcumin on macrophage involved, wear particle-induced osteolysis and its mechanism. MATERIAL AND METHODS RAW264.7 macrophages were used to test the effects of polyethylene (PE) particles and curcumin on macrophage cholesterol efflux and phenotypic changes. A mouse model of PE particle-induced calvarial osteolysis was established to test the effects of curcumin in vivo. After 14 days of treatment, the bone quality of the affected areas was analyzed by micro-computed tomography (micro-CT) and histology, and the bone surrounding soft tissues were analyzed at the cellular and molecular levels. RESULTS We found that PE particles can stimulate osteoclastogenesis and produce an M1-like phenotype in macrophages in vitro. Curcumin enhanced the cholesterol efflux in macrophages, and maintained the M0-like phenotype under the influence of PE particles in vitro. Additionally, the cholesterol transmembrane regulators ABCA1, ABCG1, and CAV1 were enhanced by curcumin in vivo. We also found enhanced bone density, reduced osteoclastogenesis, and fewer inflammatory responses in the curcumin treated groups in our mouse osteolysis model. CONCLUSIONS Our study findings indicated that curcumin can inhibit macrophage involved osteolysis and inflammation via promoting cholesterol efflux. Maintaining the cholesterol efflux might be a potential strategy to prevent periprosthetic osteolysis after total joint arthroplasty surgery.