Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1–34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1–34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1β-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.

Knee osteoarthritis (KOA) is a highly prevalent musculoskeletal disorder characterized by degeneration of cartilage and abnormal remodeling of subchondral bone (SCB). Teriparatide (PTH (1–34)) is an effective anabolic drug for osteoporosis (OP) and regulates osteoprotegerin (OPG)/receptor activator of nuclear factor ligand (RANKL)/RANK signaling, which also has a therapeutic effect on KOA by ameliorating cartilage degradation and inhibiting aberrant remodeling of SCB. However, the mechanisms of PTH (1–34) in treating KOA are still uncertain and remain to be explored. Therefore, we compared the effect of PTH (1–34) on the post-traumatic KOA mouse model to explore the potential therapeutic effect and mechanisms. In vivo study, eight-week-old male mice including wild-type (WT) (n ​= ​54) and OPG^−/− (n ​= ​54) were investigated and compared. Post-traumatic KOA model was created by destabilization of medial meniscus (DMM). WT mice were randomly assigned into three groups: the sham group (WT-sham; n ​= ​18), the DMM group (WT-DMM; n ​= ​18), and the PTH (1–34)-treated group (WT-DMM ​+ ​PTH (1–34); n ​= ​18). Similarly, the OPG^−/− mice were randomly allocated into three groups as well. The designed mice were executed at the 4th, 8th, and 12th weeks to evaluate KOA progression. To further explore the chondro-protective of PTH (1–34), the ATDC5 chondrocytes were stimulated with different concentrations of PTH (1–34) in vitro. Compared with the WT-sham mice, significant wear of cartilage in terms of reduced cartilage thickness and glycosaminoglycan (GAG) loss was detected in the WT-DMM mice. PTH (1–34) exhibited cartilage-protective by alleviating wear, retaining the thickness and GAG contents. Moreover, the deterioration of the SCB was alleviated and the expression of PTH1R/OPG/RANKL/RANK were found to increase after PTH (1–34) treatment. Among the OPG^−/− mice, the cartilage of the DMM mice displayed typical KOA change with higher OARSI score and thinner cartilage. The damage of the cartilage was alleviated but the abnormal remodeling of SCB didn't show any response to the PTH (1–34) treatment. Compared with the WT-DMM mice, the OPG^−/−-DMM mice caught more aggressive KOA with thinner cartilage, sever cartilage damage, and more abnormal remodeling of SCB. Moreover, both the damaged cartilage from the WT-DMM mice and the OPG^−/−-DMM mice were alleviated but only the deterioration of SCB in WT-DMM mice was alleviated after the administration of PTH (1–34). In vitro study, PTH (1–34) could promote the viability of chondrocytes, enhance the synthesis of extracellular matrix (ECM) (AGC, COLII, and SOX9) at the mRNA and protein level, but inhibit the secretion of inflammatory cytokines (TNF-α and IL-6). Both wear of the cartilage was alleviated and aberrant remodeling of the SCB was inhibited in the WT mice, but only the cartilage-protective effect was observed in the OPG^−/− mice. PTH (1–34) exhibited chondro-protective effect by decelerating cartilage degeneration in vivo as well as by promoting the proliferation and enhancing ECM synthesis of chondrocytes in vitro. The current investigation implied that the rescue of the disturbed SCB is dependent on the regulation of OPG while the chondro-protective effect is independent of modulation of OPG, which provides proof for the treatment of KOA. Systemic administration of PTH (1-34) could exert a therapeutic effect on both cartilage and SCB in different mechanisms to alleviate KOA progression, which might be a novel therapy for KOA.

Joint Diseases and Related Surgery (JDRS), the official journal of the Turkish Joint Diseases Foundation, is an international, peer-reviewed, immediate open access journal. All published articles in JDRS has been free for everyone, without embargo, since 1990.

BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty (pTHA). However, the literature demonstrates significant variability regarding the relative contributions of different factors. AIM To investigate the key determinants of aseptic loosening, we performed a systematic review and meta-analysis. METHODS A comprehensive search of PubMed, Web of Science, EMBASE, and the Cochrane Library was conducted, encompassing studies from database inception to January 1, 2025. Meta-analyses were performed to evaluate factors associated with aseptic loosening following pTHA. Inclusion and exclusion criteria were systematically applied at each stage to ensure methodological transparency and reproducibility. Study quality was assessed using standardized categories. Pooled odds ratio (OR) with corresponding 95% confidence interval were calculated with random- or fixed-effects models to generate reliability estimates, and study heterogeneity was visualized using forest plots. Ten factors, categorized into patient-, surgeon-, and device-related domains, were reviewed and meta-analyzed. Funnel plot analysis demonstrated a relatively symmetrical distribution, suggesting minimal publication bias. RESULTS A meta-analysis of 20 studies (520789 participants) found a pooled prevalence of 1.96%. Significant risk factors for aseptic loosening after pTHA included elevated body mass index (OR = 1.116, P < 0.001), higher Charlson comorbidity index (OR = 1.378, P < 0.001), prosthesis-related factors (OR = 1.497, P < 0.001), and adverse lifestyles (OR = 2.198, P = 0.037). Protective factors were non-white race (OR = 0.445, P < 0.001) and favorable genetics (OR = 0.723, P < 0.001). Male sex increased risk (OR = 1.232, P = 0.016), while age and anatomy were not significant. Surgical expertise showed a slight protective effect (OR = 1.048, P < 0.001). A comprehensive understanding of the modifiable and non-modifiable factors contributing to aseptic loosening after pTHA requires consideration of patient-related factors, surgical expertise, and prosthesis characteristics. CONCLUSION The identification of these factors is critical for risk mitigation. High-risk patients should receive targeted counseling regarding individualized profiles. Further studies are warranted to establish clearer causal relationships and identify additional contributing factors.

Sarcopenia is an age-related progressive muscle degeneration condition characterized by loss of muscle mass, muscle strength, and poor physical function. Its prevalence and mortality rates continue to rise with advancing age, significantly impairing patients' quality of life. The pathogenesis of sarcopenia involves multiple pathophysiological processes, including imbalanced protein catabolism, cell death, mitochondrial dysfunction, and various cellular signaling pathways. Therefore, it is crucial to identify potential therapeutic targets and treatments for sarcopenia. As an exercise-induced myokine, irisin has shown great potential in maintaining skeletal muscle health. In this review, we focus on the relationship between irisin and sarcopenia, delving into existing research to elucidate irisin's mechanisms of action in sarcopenia—including its effects on protein catabolism, cell death, mitochondrial dysfunction, cellular signaling, and muscle cell proliferation and differentiation. We provide insights into irisin as a therapeutic intervention for sarcopenia and provide essential evidence to support its clinical application in sarcopenia treatment.