Skeletal fracture healing involves a variety of cellular and molecular events; however, the mechanisms behind these processes are not fully understood. In the current study, we investigated the potential involvement of the signal transducer and activator of transcription 1 (STAT1), a critical regulator for both osteoclastogenesis and osteoblast differentiation, in skeletal fracture healing. We used a fracture model and a cortical defect model in mice, and found that fracture callus remodeling and membranous ossification are highly accelerated in STAT1-deficient mice. Additionally, we found that STAT1 suppresses Osterix transcript levels and Osterix promoter activity in vitro, indicating the suppression of Osterix transcription as one of the mechanisms behind the inhibitory effect of STAT1 on osteoblast differentiation. Furthermore, we found that fludarabine, a potent STAT1 inhibitor, significantly increases bone formation in a heterotopic ossification model. These results reveal previously unknown functions of STAT1 in skeletal homeostasis and may have important clinical implications for the treatment of skeletal bone fracture. ß

Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG), a decoy receptor of RANKL, maintain bone mass by regulating the differentiation of osteoclasts, which are bone-resorbing cells. Endochondral bone ossification and bone fracture healing involve cartilage resorption, a less well-understood process that is needed for replacement of cartilage by bone. Here we describe the role of OPG produced by chondrocytes in chondroclastogenesis. Fracture healing in OPG(-/-) mice showed faster union of the fractured bone, faster resorption of the cartilaginous callus, and an increased number of chondroclasts at the chondroosseous junctions compared with that in wild-type littermates. When a cultured pellet of OPG(-/-) chondrocytes was transplanted beneath the kidney capsule, the pellet recruited many chondroclasts. The pellet showed the ability to induce tartrate-resistant acid phosphatase-positive multinucleated cells from RAW 264.7 cells in vitro. Finally, OPG(-/-) chondrocytes (but not wild-type chondrocytes) cultured with spleen cells induced many tartrate-resistant acid phosphatase-positive multinucleated cells. The expression of RANKL and OPG in chondrocytes was regulated by several osteotropic factors including 1,25-dihydroxyvitamin D(3), PTHrP, IL-1alpha, and TNF-alpha. Thus, local OPG produced by chondrocytes probably controls cartilage resorption as a negative regulator for chondrocyte-dependent chondroclastogenesis.

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Severe arthritis or derangement of the distal radioulnar joint (DRUJ) leads to instability of the DRUJ, and the subluxation of the ulna causes pain on motion, loss of grip strength, and a restriction of forearm rotation. 1 A variety of surgical procedures have been described to treat these. 2 In 1912, Darrach described a resection of the ulnar head. 3 Although this procedure could successfully restore forearm rotation, serious postoperative complications frequently occurred, such as a further loss of grip strength or pain over the proximal ulnar stump. [4][5][6] As an alternative solution, Sauvé and Kapandji described a distal radioulnar arthrodesis combined with an intentional pseudarthrosis of the distal ulna. 7 Some reports of this technique have shown superior results both clinically and radiographically, [8][9][10][11] and hence the Sauvé-Kapandji (S-K) procedure has almost replaced Darrach's as the most common resection arthroplasty for the treatment of DRUJ dysfunction. The conventional S-K procedure is contraindicated, however, in patients with extremely poor bone quality, which AbstractPurpose The Sauvé-Kapandji (S-K) procedure is now an established treatment option for symptomatic distal radioulnar joint (DRUJ) dysfunction. However, for patients with poor bone quality (frequently as a result of advanced-stage rheumatoid arthritis [RA]), the conventional S-K procedure is difficult to perform without reducing the radioulnar diameter of the wrist, which may result in a loss of grip strength and pain over the proximal ulnar stump. The purpose of this study was to review the radiographic outcomes of patients who underwent a modified S-K procedure that involves rotating the resected ulnar segment 90 degrees and using it to bridge the gap between the sigmoid notch and the ulnar head. Methods The modified S-K procedure was performed in 29 wrists of 23 patients. Twenty-one patients had severe RA, while two had malunited radius fractures. The mean follow-up period was 43 months (range, 23 to 95). The radiographic evaluation included a measurement of the radioulnar width, the pseudarthrosis gap between the proximal and distal ulnar stump, the radioulnar distance, and the ulnar translation of the carpus. Results The radioulnar width of the wrist, pseudarthrosis gap, and radioulnar distance were well maintained throughout the period. A postoperative loss in the radioulnar width of the wrists appeared to correlate with a postoperative additional ulnar translocation of the carpus. Conclusion Narrowing of the radioulnar width of the wrist is a potential cause of progressive ulnar translocation of the carpus. The modified technique for the S-K procedure maintains the distal ulna in the proper position and provides sufficient ulnar support for the carpus. It is a useful reconstruction procedure in patients with severe RA with poor bone quality.

Cases of infection with hypervirulent Klebsiella pneumoniae are gradually increasing in number, and cause life-threatening community-acquired infection even in immunocompetent patients. A 14-year-old boy developed septic hip arthritis due to hypervirulent K. pneumoniae (sequence type 23, serotype K1, magA positive). The patient initially seemed to have been successfully treated with antibiotics and surgical intervention, but septic arthritis developed into osteomyelitis of the femoral head and myositis, which required long-term antibiotic therapy and additional surgical intervention. This is the first pediatric case of hypervirulent K. pneumoniae septic hip arthritis. Treatment plans should mainly consist of antibiotic therapy and surgical intervention. Clinicians, even pediatricians, in developed countries should be aware of the increasing incidence of hypervirulent Klebsiella pneumoniae infection.