ObjectiveTo elucidate the role of interleukin-33 (IL-33) in glucocorticoid-induced osteonecrosis of the femoral head (ONFH) in mice, with particular emphasis on its effects on bone remodeling, inflammatory regulation, and fibrosis. Methods In vivo: Fifteen 9-week-old male C57BL/6J wild-type mice were randomly divided into a normal control group, an ONFH group, and an intervention group, with 5 mice in each group. A glucocorticoid-induced ONFH model was established in the ONFH group and intervention group using a combined administration of lipopolysaccharide and methylprednisolone. The intervention group received intraperitoneal injection of IL-33 for 4 consecutive days during the early stage of model establishment; the normal control group received saline injection at the same time points. General conditions of mice were observed during the experiment. Endogenous IL-33 and transmembrane ST2 (ST2 ligand, ST2L) expression in the femoral head was assessed via immunofluorescence, quantitative PCR (qPCR), and Western blot. Bone necrosis and fibrosis were evaluated using HE and Masson staining. Immunohistochemistry was performed to detect osteogenic markers [osteocalcin (OCN), osteopontin (OPN), Runt-related transcription factor 2 (Runx2)] and osteoclastic marker (receptor activator of nuclear factor-κB ligand, RANKL), while serum cytokine levels [tumor necrosis factor (TNF-α), IL-6, IL-1β, IL-4, IL-10] were quantified by ELISA. In vitro: Murine osteoblasts were divided into control group (DMEM+PBS), IL-33 group (DMEM+10 ng/mL IL-33), and IL-33+ST2L group (DMEM+10 ng/mL IL-33+1 μg/mL ST2L antibody). After corresponding treatment, cell proliferation was detected by EdU incorporation assay. Additional osteoblasts were subjected to osteogenic induction culture, and mineralization, and the expression of osteogenesis-related genes (Runx2, collagen type Ⅰ, OCN, and OPN) were assessed by using alkaline phosphatase (ALP) staining, Alizarin red staining, and qPCR, respectively. Results In vivo: All animals survived until the completion of the experiment. Mice in the intervention group and ONFH group showed restricted mobility. Compared with the normal control group, the expressions of IL-33 and ST2L significantly upregulated at both mRNA and protein levels (P<0.05). Exogenous IL-33 administration exacerbated, rather than ameliorated, trabecular destruction and fibrosis, with the intervention group showing significantly increased fibrosis area percentage and empty lacunae rate compared with the other two groups (P<0.05). Furthermore, IL-33 treatment further suppressed the expressions of osteogenic markers (Runx2, OCN, OPN) while significantly enhancing the expression of the osteoclastic marker (RANKL) (P<0.05). ELISA results showed that compared with the ONFH group, serum levels of pro-inflammatory cytokines (IL-4, IL-6, IL-1β) were significantly lower in the intervention group (P<0.05). In vitro: Compared with control group, IL-33 significantly impaired osteoblast proliferation and differentiation, as evidenced by reduced cell proliferation rate, decreased ALP activity, and reduced calcium nodule formation (P<0.05). The expression of osteogenesis-related genes was also suppressed, with significant differences between groups (P<0.05). ST2L blockade effectively reversed these IL-33-mediated suppressive effects, leading to significant recovery of osteoblast proliferation and differentiation (P<0.05). Notably, the mRNA expression levels of collagen typeⅠand OCN were restored to normal (P>0.05). ConclusionIL-33 exacerbates ONFH by impairing osteoblast viability and function and inhibiting bone regeneration. Targeting the IL-33/ST2L signaling axis may represent a promising novel therapeutic strategy for ONFH.
Objective To compare the effects of double-channel core decompression (CD) combined with medullary cavity irrigation with those of simple CD on progression of collapse and clinical outcomes in non-traumatic osteonecrosis of the femoral head (ONFH). Methods A retrospective analysis was conducted on the clinical data of 19 patients (30 hips) with non-traumatic ONFH who underwent double-channel CD combined with medullary cavity irrigation and admitted between January 2024 and October 2024 (CD+irrigation group). According to a 1: 2 ratio, 54 patients (60 hips) who underwent simple CD and were matched in terms of age, gender, and body mass index (BMI) were included as the control (CD group). There was no significant difference in baseline data such as age, gender, BMI, affected side, ONFH type, preoperative Association Research Circulation Osseous (ARCO) stage, bone marrow edema stage, visual analogue scale (VAS) score for pain, and Harris score between the two groups (P>0.05). The postoperative discharge time and occurrence of complications were recorded for both groups. The VAS scores before operation and at discharge after operation were compared, and the differences between pre- and post-operation (change values) were calculated for intergroup comparison. The Harris scores before operation and at discharge and 3 months after operation were also compared. During follow-up, X-ray film, CT, and MRI were performed for reexamination. The ARCO stage and bone marrow edema stage were evaluated at 3 months after operation and compared with those before operation to determine whether there was radiological progression or relief. Results All incisions in both groups healed by first intention after operation, with no infection, femoral neck fracture, or other operation-related complications. All patients were followed up, and the follow-up time of the CD+irrigation group was (146.8±27.7) days, and that of the CD group was (164.3±48.2) days; there was no significant difference between the two groups (t=1.840, P=0.069). There was no significant difference in the length of hospital stay between the two groups (P>0.05). At discharge after operation, the VAS score of the CD+irrigation group was significantly lower than that of the CD group (P<0.05), and the change value was significantly higher than that of the CD group (P<0.05). The Harris scores at discharge and 3 months after operation in the CD+irrigation group were significantly higher than those in the CD group (P<0.05). The Harris score gradually increased with time, and the differences between different time points were significant (P<0.05). Radiological reexamination showed that there was no significant difference in the ARCO stage and the incidence of radiological progression between the two groups at 3 months after operation (P>0.05); however, the bone marrow edema stage and the degree of bone marrow edema relief in the CD+irrigation group were better than those in the CD group, with significant differences (P<0.05).Conclusion Double-channel CD combined with medullary cavity irrigation can significantly alleviate hip joint pain and improve joint function in patients with non-traumatic ONFH, reduce the degree of bone marrow edema in the femoral head, and delay the progression of ONFH.