Mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple lineages, making MSC transplantation a promising option for bone regeneration. Both matricellular proteins and growth factors play an important role in regulating stem cell fate. In this study, we investigated the effects of matricellular protein SMOC2 (secreted modular calcium-binding protein 2) on bone morphogenetic protein 9 (BMP9) in mouse embryonic fibroblasts (MEFs) and revealed a possible molecular mechanism underlying this process. We found that SMOC2 was detectable in MEFs and that exogenous SMOC2 expression potentiated BMP9-induced osteogenic markers, matrix mineralization, and ectopic bone formation, whereas SMOC2 knockdown inhibited these effects. BMP9 increased the levels of p-FAK and p-AKT, which were either enhanced or reduced by SMOC2 and FAK silencing, respectively. BMP9-induced osteogenic markers were increased by SMOC2, and this increase was partially abolished by silencing FAK or LY290042. Furthermore, we found that general transcription factor 2I (GTF2I) was enriched at the promoter region of SMOC2 and that integrin β1 interacted with SMOC2 in BMP9-treated MEFs. Our findings demonstrate that SMOC2 can promote BMP9-induced osteogenic differentiation by enhancing the FAK/PI3K/AKT pathway, which may be triggered by facilitating the interaction between SMOC2 and integrin β1.

Benign lesions of the spine include benign tumors and tumor-like lesions of the spine, which usually occur in the thoracic and lumbar vertebrae. The incidence rate is low, accounting for about 1% of primary bone tumors. Few cases of endoscopic treatment of benign spinal lesions have been reported in the literature. Here, we introduce a new surgical technique using full endoscopy and allogeneic bone grafting to treat benign spinal lesions. All patients in this study successfully underwent the operation, and their pain was significantly relieved postoperatively. The patient VAS scores decreased from 3.07 ± 0.70 preoperatively to 0.33 ± 0.49 at the last follow-up visit (p < 0.05). The mean total blood loss (including drainage blood) was 16.67 ± 6.98 mL. The mean operative time was 63.33 ± 7.23 min. No patients developed numbness in the corresponding segmental distribution after surgery, none of the patients had serious postoperative complications, and none had focal recurrence during follow-up requiring reoperation. Patients reported symptom relief throughout the whole follow-up period. We believe that endoscopic surgery preserves the ligaments and soft tissues around the vertebral body, and that this technique is feasible with minimal trauma, rapid recovery, and good outcomes at short-term follow-up. This minimally invasive treatment modality offers a new option for the treatment of patients with benign spinal lesions.

Bone morphogenetic protein 9 (BMP9) is a cytokine with potent osteoinductive activity, although its precise regulatory mechanisms remain incompletely elucidated. NOTUM, a secreted palmitoleoyl-protein carboxylesterase, has an unclear role in osteogenic differentiation. This study aims to explore the role and mechanism of NOTUM in BMP9-induced osteogenic differentiation of mouse embryonic fibroblasts (MEFs). In the BMP9-induced osteogenic differentiation model, Notum was either overexpressed or silenced, and the expression of RUNX2 and OPN as well as osteogenic signaling pathways were assessed by q-PCR and Western blot. ALP staining and Alizarin Red staining were subsequently performed to determine ALP activity and matrix mineralization. Furthermore, the osteogenic effect of Notum was evaluated using an in vivo subcutaneous ectopic osteogenesis model, supplemented by histochemical staining and micro-CT analysis. BMP9 significantly downregulates NOTUM protein expression in MEF cells. NOTUM attenuated BMP9-induced expression of osteogenic markers RUNX2 and OPN, as well as ALP activity and matrix mineralization. In vivo ectopic osteogenesis assays yielded results consistent with in vitro observations. Mechanistically, NOTUM overexpression reduced β-catenin protein levels, while NOTUM knockdown elevated β-catenin accumulation during BMP9-mediated osteogenic differentiation. NOTUM overexpression up-regulated GSK-3β protein expression while suppressing its phosphorylation status during BMP9-induced osteogenesis, whereas NOTUM depletion produced the converse effects. Pharmacological activation of the Wnt/β-catenin signaling pathway rescued osteogenic marker expression, effectively counteracting NOTUM-mediated suppression of BMP9's osteogenic potential. NOTUM serves as a novel regulator of BMP9-Induced osteogenesis via modulation of the Wnt/β-Catenin Axis, Suggesting its potential as a therapeutic target for bone regeneration.

Osteosarcoma (OS) is a highly aggressive primary bone malignancy that predominantly affects children and adolescents. Although surgical intervention and neoadjuvant therapy demonstrate efficacy in localized OS, postoperative survival rates remain suboptimal for patients with metastatic and recurrent OS. In recent years, immunotherapy has garnered considerable attention due to its promising efficacy across various solid tumors. However, the distinct immunosuppressive tumor microenvironment in OS restricts therapeutic response, as immunosuppressive states are further intensified in metastatic and recurrent lesions, thereby complicating immunotherapy efforts. Recent studies have found that metabolic reprogramming plays a crucial role in shaping the immunosuppressive tumor microenvironment of OS. Tumor cells can induce adaptive metabolic changes in immune cells through competitively consuming nutrients, accumulating immunosuppressive metabolites, and secreting exosomes. This subsequently diminishes their immune functions and promotes immune escape, which partially explains the poor efficacy of immunotherapy in OS. Thus, combining immunotherapy and metabolic-targeted drugs is a potential strategy for enhancing treatment efficacy against OS. This review focuses on the major characteristics of the immunosuppressive microenvironment in OS. It details how metabolic reprogramming in glucose, lipid, and amino acid metabolism remodels this environment and influences key immune cells, including tumor-associated macrophages (TAMs), T cells, and natural killer (NK) cells. It further explores the translational potential of combining metabolic interventions with immunotherapy to advance the clinical application in OS.

Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis, which characterized by the decreased bone strength and increased frac