Inhibition of microRNA-222 expression accelerates bone healing with enhancement of osteogenesis, chondrogenesis, and angiogenesis in a rat refractory fracture model.

BACKGROUND: It is difficult to achieve bone union in case of non-union with non-invasive techniques. MicroRNAs (miRNAs) are short, non-coding RNAs that act as repressors of gene expression at the level of post-transcriptional regulation. This study focuses on microRNA (miR)-222 as it is known to be a negative modulator of angiogenesis, an essential component of fracture healing. The purpose of this study was to analyze the effects of miR-222 on osteogenic and chondrogenic differentiation in human mesenchymal stromal cell (MSC)s in vitro, and to determine whether local administration of miR-222 inhibitor into the fracture site could achieve bone union in vivo. METHOD: miR-222 expression in human bone marrow mesenchymal stem cells (hMSCs), and osteogenic differentiation in hMSCs, were investigated. The gain or loss of miR-222 function was examined, in order to assess the effects of miR-222 on osteogenic and chondrogenic differentiation in hMSCs. A femoral transverse fracture was completed in rats, and the periosteum at the fracture site was cauterized. Then, either an miR-222 inhibitor or an miR-222 mimics, mixed with atelocollagen, was administered into the fracture site. A non-functional inhibitor negative control was administered to the control group. At 2, 4, 6, and 8 weeks, radiographs of the fractured femurs were obtained. Immunohistochemistry was performed at 2 weeks to evaluate the capillary density. At 8 weeks, micro-computed tomography (µCT) imaging analysis and histological evaluations were performed. RESULTS: The expression of miR-222 significantly decreased as osteogenic differentiation of hMSCs proceeded. Inhibition of miR-222 promoted osteogenic differentiation, and over expression of miR-222 inhibited osteogenic differentiation in hMSCs, which was confirmed by measuring expression of Runx2, collagen type 1A1 (COL1A1), and osteocalcin. Inhibition of miR-222 promoted chondrogenic differentiation in hMSCs, which was confirmed by measuring expression of collagen type II (COL2A1), aggrican, and SOX9. Bone union at the fracture site was achieved in only the groups treated with the miR-222 inhibitor, confirmed by radiographic, µCT and histological evaluation at 8 weeks after administration. Immunohistochemistry showed that capillary density in the miR-222 inhibitor group was significantly higher than that in the control group and in the miR-222 mimics group. CONCLUSION: Local administration of miR-222 inhibitor can accelerate bone healing by enhancing osteogenesis, chondrogenesis, and angiogenesis in the rat refractory model.

Low femoral antetorsion as a risk factor for bony impingement after bipolar hemiarthroplasty.

INTRODUCTION: Reports of dislocation after bipolar hemiarthroplasty (BHA) abound in literature, and several studies have mentioned the factors that are associated with an increased risk of dislocation. However, there is no report detailing the pattern of impingement in BHA and how femoral antetorsion can affect the range of motion (ROM) after BHA. PURPOSE: The purpose of this study was to evaluate the pattern of impingement in BHA and whether femoral antetorsion affects the ROM after BHA using three-dimensional (3D) dynamic motion analysis. METHODS: Using the computed tomography (CT) data of 60 patients (60 hips), including 31 men and 29 women who underwent BHA for the treatment of idiopathic osteonecrosis (ION) of the femoral head, we calculated the antetorsion of the femoral neck, ROM of flexion (Flex), internal rotation (Int-R), and external rotation (Ext-R) using a CT-based 3D simulation software. We evaluated the pattern of impingement and the relationship between femoral antetorsion and ROM in BHA. As for the implant position in the 3D simulation software, the anteversion of the femoral implant was set to be the same as the natural antetorsion of the femoral neck and neck length was set to be the standard neck in all cases. RESULTS: This study revealed the mechanism of impingement in BHA: (1) bone to bone impingement and (2) implant to bone impingement. We found a significant decrease in the ROM of Flex and Int-R inversely proportional to the femoral antetorsion. In patients with lower femoral antetorsion, the ROM of Flex and Int-R decreased due to bony impingement (the anterior great trochanteric region of the femur impinges on the anteroinferior edge of the anteroinferior iliac spine). Whereas, high anteversion of the femoral implant may decrease the ROM of Ext-R; however, our results also showed that even the lowest ROM of Ext-R with 10° hip extension was over 40°. CONCLUSIONS: We demonstrated that lower femoral antetorsion substantially affects the ROM of Flex and Int-R due to bony impingement. For these patients, there should be consideration given to retaining femoral "anterior offset" in BHA.

Inclusion and Exclusion Criteria in the Diagnosis of Femoroacetabular Impingement.

PURPOSE: The purpose of this study was to clarify the criteria for femoroacetabular impingement (FAI) by way of a systematic review of FAI-related articles, as well as to define more appropriate inclusion or exclusion criteria in the diagnosis of FAI. METHODS: A systematic review of FAI-related articles was performed using Web of Science. Thirty-two articles met the inclusion and exclusion criteria. In these articles we investigated radiographic findings for the diagnosis of FAI and the prevalence of each FAI-related finding. RESULTS: The crossover sign was used in 22 articles (69%); acetabular index, 9 articles (28%); posterior wall sign, 7 articles (22%); and prominence of the ischial spine sign, 3 articles (7%). Regarding acetabular coverage, the lateral center-edge (LCE) angle was described in 13 articles (41%), in which an LCE angle either of more than 40° or of more than 30° combined with an acetabular index of less than 0° was considered an inclusion criterion for pincer impingement. Meanwhile, the alpha angle was used in 28 articles (88%), in which 50° or 55° was recommended as a positive finding of cam impingement. CONCLUSIONS: Common findings of pincer or cam deformity were used to select FAI patients with sufficient coverage of the acetabulum with an LCE angle of more than 25°. Patients with an LCE angle of less than 25° or those with local acetabular deficiency regardless of having a normal LCE angle should be excluded from the FAI criteria, even if the FAI-related findings are positive. LEVEL OF EVIDENCE: Level IV, systematic review of Level I through IV studies.