MicroRNA-21-5p as a novel therapeutic target for osteoarthritis.

OBJECTIVE: Growing evidence indicates that microRNAs (miRNA) play a critical role in the pathogenesis of OA, and overexpressing or silencing miRNA expression in OA models can contribute to the development of miRNA-based therapeutics. The objective of this study was to determine whether intra-articular injection of miRNA can inhibit OA progression. METHODS: The miRNA expression profile was determined in OA cartilage tissues and controls. Functional analysis of the miRNAs on extracellular matrix degradation was performed after miRNA mimic or inhibitor transfection. Luciferase reporter assays and western blotting were employed to determine miRNA targets. To investigate the functional mechanism of miR-21-5p in OA development, miR-21-5pfl/flCol2a1-CreER and wild-type mice were subject to surgical destabilization of the medial meniscus. Therapeutically, wild-type mice undergoing surgical destabilization of the medial meniscus were treated with intra-articular injection of agomir- and antagomir-21-5p. RESULTS: We found that expression of miR-21-5p was significantly up-regulated in OA cartilage tissues. The articular cartilage degradation of miR-21-5p conditional knockout mice was significantly alleviated compared with that of wild-type mice in spontaneous and destabilization of the medial meniscus models. Through gain-of-function and loss-of-function studies, miR-21-5p was shown to significantly affect matrix synthesis genes expression, and chondrocyte proliferation and apoptosis. Further, fibroblast growth factor 18 (FGF18) was identified as a target of miR-21-5p. Intra-articular injection of antagomir-21-5p significantly attenuated the severity of experimental OA. Clinically, FGF18 expression level was correlated with miR-21-5p expression and a modified Mankin scale. CONCLUSION: Our findings reveal a miRNA functional pathway important for OA development, highlighting miRNA-21-5p silencing as an attractive therapeutic regimen in future clinical trials involving patients with OA.

Anatomical study based on 3D-CT image reconstruction of the hip rotation center and femoral offset in a Chinese population: preoperative implications in total hip arthroplasty.

BACKGROUND: Several anatomical studies regarding the value of hip rotation center (HRC) and femoral offset (FO) have been performed in Western populations. However, there are a few data on hip morphological values in the Chinese population based on CT scans. This study measured the values of the hip and pelvis, especially HRC and FO, in a Chinese population and compared them with the published values obtained from Western populations. PATIENTS AND METHODS: One hundred patients (50 females and 50 males) were included in the present study, and 3D-CT reconstructions of the hip and pelvis were generated. The mean age was 51.4 ± 8.9 years and mean body mass index (BMI) was 23.5 ± 2.6 kg/m2. All the morphologic measurements were compared between genders and sides, and the relationships between different parameters were analyzed. RESULTS: The mean FO values were 38.4 ± 4.7 mm and 35.6 ± 4.4 mm for the males and females, respectively. A significant negative correlation was noted between FO and neck shaft angle (NSA) in both genders (r = - 0.262, P = 0.009 for the males, r = - 0.350, P ≤ 0.001 for the females). A significant positive correlation was found between horizontal distance (HD) and diameter of the femoral head (DFH) in both genders (r = 0.734, P ≤ 0.001 for the males, r = 0.658, P ≤ 0.001 for the females). A significant positive correlation was noted between HD and pelvic width (PW) in males (r = 0.455, P ≤ 0.001). A significant positive correlation was also noted between HD and pelvic height (PH) in males (r = 0.318, P ≤ 0.001). A significant positive correlation was observed between FO and pelvic cavity height (PCH) in males (r = 0.411, P ≤ 0.001), and a significant positive correlation was observed between VD and PCH in females (r = 0.497, P ≤ 0.001). The tip of the greater trochanter was, on average, 7.0 mm higher than the femoral head center. Relationships between DFH and pelvic morphometric parameters were also observed. CONCLUSION: The present morphological data and the relationships between them can be applied to design better ethnic-specific THA prostheses and preoperative plans.

Does subcutaneous administration of recombinant human erythropoietin increase thrombotic events in total hip arthroplasty? A prospective thrombelastography analysis.

BACKGROUND: Anemia is one of severe complications in the perioperative period of total hip arthroplasty (THA). Erythropoietin (EPO) has been considered to improve patients' anemia state, but its efficiency and safety remains controversial. METHODS: A total of 152 patients who underwent total hip arthroplasty from January 2017 to March 2019 were randomized to 2 groups. Recombinant human erythropoietin (rHu-EPO) group was treated with rHu-EPO subcutaneous injection 10000 IU after operation and once daily in the next week, while control group was treated with none extra treatment. Routine hematologic examination and thrombelastography (TEG) performed at different time point respectively. Doppler ultrasound for bilateral lower limbs was performed 1 day before surgery and 7 days after surgery. Auxiliary examination outcomes, blood transfusions outcomes, and postoperative complications were recorded as assessment indicators. RESULTS: The difference in the relevant indexes of traditional coagulation and TEG values between two groups were not significantly. No significant difference was observed in the incidence of thromboembolism events and other complications between two groups during postoperative period. The amount of intraoperative blood loss was similar between the two groups. However, the postoperative use and dosage of allogeneic blood in the rHu-EPO group were lower than those in the control group. The hemoglobin and hematocrit level in the rHu-EPO group were higher than that in the control group after surgery. CONCLUSION: Postoperative subcutaneous injection of rHu-EPO can improve hematological anemia-related parameters, reduce the use and dosage of allogeneic blood transfusions (ABTs), and has no significant influence on the formation of thrombosis and other complications in patients undergoing total hip arthroplasty in short term.