Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone

BACKGROUND: Giant cell tumors (GCTs) of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells (MNCs). Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells, while monocyte-like cells and MNCs are reactive osteoclast precursor cells (OPCs) and osteoclasts (OCs), respectively. In this study, we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor (VEGF)-Flt-1 (type-1 VEGF receptor)-focal adhesion kinase (FAK) pathway. METHODS: The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry. RESULTS: In GCT samples, CD68, a marker of OPCs and OCs, co-localized with Flt-1. Conditioned media from GCT tissue (GCT-CM) enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover, there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK. CONCLUSIONS: Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs

Bone fragility via degradation of bone quality featured by collagen/apatite micro-arrangement in human rheumatic arthritis

Although increased bone fragility is a well-recognized consequence in patients with rheumatoid arthritis (RA), the essential cause of degenerate bone strength remains unknown. This study aimed to determine factors contributing to bone dysfunction in RA by focusing on the bone matrix micro-arrangement, based on the preferential orientation of collagen and the related apatite c-axis as a bone quality index. The classical understanding of RA is limited to its severe pathological conditions associated with inflammation-induced bone loss. This study examined periarticular proximal tibiae from RA patients as compared with osteoarthritis (OA) patients as controls. Bone tissue material strength was disrupted in the RA group compared with the control. Collagen/apatite micro-arrangement and vBMD were significantly lower in the RA group, and the rate of decrease in apatite c-axis orientation (−45%) was larger than that in vBMD (−22%). Multiple regression analysis showed that the degree of apatite c-axis orientation (β = 0.52, p = 1.9 × 10−2) significantly contributed to RA-induced bone material impairment as well as vBMD (β = 0.46, p = 3.8 × 10−2). To the best of our knowledge, this is the first report to demonstrate that RA reduces bone material strength by deteriorating the micro-arrangement of collagen/apatite bone matrix, leading to decreased fracture resistance. Our findings represent the significance of bone quality-based analysis for precise evaluation and subsequent therapy of the integrity and soundness of the bone in patients with RA.Ozasa R., Matsugaki A., Ishimoto T., et al. Bone fragility via degradation of bone quality featured by collagen/apatite micro-arrangement in human rheumatic arthritis. Bone, 155, 116261. https://doi.org/10.1016/j.bone.2021.116261

Reconstruction of Acute Patellar Tendon Rupture after Patellectomy

Acute rupture of the knee extensor mechanism after patellectomy is extremely rare. We present the case of a patient with acute patellar tendon rupture who had undergone patellectomy 53 years before. Twelve days after the injury, the ruptured patellar tendon was repaired with end-to-end suture. Postoperatively, we splinted the knee for 6 weeks but permitted the patient to walk without limiting weight bearing at 1 week postoperatively. At one-year follow-up, the patient is able to move his knee almost full range of motion and the Lysholm knee score is 81. The patient is satisfied with the outcome. This is the first report to treat acute rupture of the patellar tendon in a patient who had undergone patellectomy. Although careful rehabilitation is required, end-to-end suture might be an adequate surgical procedure for acute rupture of the knee extensor mechanism after patellectomy