Hironori Kakoi

Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism

Background: It is not clear how BMP-induced chondrocyte maturation is cell-autonomously terminated. Results: BMP-2 induced the ceramide-generating enzyme neutral sphingomyelinase 2 (nSMase2) in chondrocytes, whereas silencing of nSMase2 enhanced maturation in an Akt signaling-dependent manner. Conclusion: nSMase2 signaling regulates BMP-induced chondrocyte maturation as a negative feedback mechanism. Significance: This study elucidated the novel link between BMP and lipid signaling in chondrogenesis. Although bone morphogenic protein (BMP) signaling promotes chondrogenesis, it is not clear whether BMP-induced chondrocyte maturation is cell-autonomously terminated. Loss of function of Smpd3 in mice results in an increase in mature hypertrophic chondrocytes. Here, we report that in chondrocytes the Runx2-dependent expression of Smpd3 was increased by BMP-2 stimulation. Neutral sphingomyelinase 2 (nSMase2), encoded by the Smpd3 gene, was detected both in prehypertrophic and hypertrophic chondrocytes of mouse embryo bone cartilage. An siRNA for Smpd3, as well as the nSMase inhibitor GW4869, significantly enhanced BMP-2-induced differentiation and maturation of chondrocytes. Conversely, overexpression of Smpd3 or C2-ceramide, which mimics the function of nSMase2, inhibited chondrogenesis. Upon induction of Smpd3 siRNA or GW4869, phosphorylation of both Akt and S6 proteins was increased. The accelerated chondrogenesis induced by Smpd3 silencing was negated by application of the Akt inhibitor MK2206 or the mammalian target of rapamycin inhibitor rapamycin. Importantly, in mouse bone culture, GW4869 treatment significantly promoted BMP-2-induced hypertrophic maturation and calcification of chondrocytes, which subsequently was eliminated by C2-ceramide. Smpd3 knockdown decreased the apoptosis of terminally matured ATDC5 chondrocytes, probably as a result of decreased ceramide production. In addition, we found that expression of hyaluronan synthase 2 (Has2) was elevated by a loss of Smpd3, which was restored by MK2206. Indeed, expression of Has2 protein decreased in nSMase2-positive hypertrophic chondrocytes in the bones of mouse embryos. Our data suggest that the Smpd3/nSMase2-ceramide-Akt signaling axis negatively regulates BMP-induced chondrocyte maturation and Has2 expression to control the rate of endochondral ossification as a negative feedback mechanism.

Pathological femoral fractures due to osteomalacia associated with adefovir dipivoxil treatment for hepatitis B: a case report

We present a case of a 62-year-old man who underwent total hip arthroplasty for treatment of pathologic femoral neck fracture associated with adefovir dipivoxil-induced osteomalacia. He had a 13-month history of bone pain involving his shoulders, hips, and knee. He received adefovir dipivoxil for treatment of lamivudine-resistant hepatitis B virus infection for 5 years before the occurrence of femoral neck fracture. Orthopedic surgeons should be aware of osteomalacia and pathological hip fracture caused by drug-induced renal dysfunction, which results in Fanconi’s syndrome.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1600344696739249

Predictive factors of mortality and deterioration in performance of activities of daily living after hip fracture surgery in Kagoshima, Japan

Given that different hospitals achieve different outcomes, optimal evaluation of treatment outcomes in the local community requires evaluation of many institutions in that area. We carried out a prospective multicenter cohort study in Kagoshima Prefecture to identify factors that contribute to deterioration in activities of daily living performance and patient mortality 1 year after surgical treatment of hip fractures.

A Kirschner wire as a transverse-axis guide to improve acetabular cup positioning

Purpose. To compare cup-positioning accuracy in total hip arthroplasty (THA) with or without use of a Kirschner wire as a transverse-axis guide for pelvic alignment. Methods. Records of 18 men and 73 women (mean age, 60 years) who underwent primary THA with (n=49) or without (n=42) use of a Kirschner wire as a transverse-axis guide for pelvic alignment were reviewed. A 2.4-mm Kirschner wire as a transverse-axis guide was inserted to the anterior superior iliac spine and was parallel to a line linking the left and right anterior superior iliac spine. The safe zone for cup positioning was defined as 30° to 50° abduction and 10° to 30° anteversion. Of the 5 operative surgeons, 2 were classified as experienced (total surgical volume >300) and 3 as inexperienced (total surgical volume of <50). The proportion of patients with the cup in the safe zone was compared in patients with or without use of the transverse-axis guide and in experienced and inexperienced surgeons. Results. For inexperienced surgeons, the use of the transverse-axis guide significantly improved the proportion of patients with the cup in the safe zone from 90% to 100% for abduction, from 50% to 82.4% for anteversion, and from 40% to 82.4% for both. Patients with the cup inside or outside the safe zone were comparable in terms of body height, weight, BMI, subcutaneous fat thickness, incision length, and acetabular cup size. Conclusion. The use of the transverse-axis guide improved the accuracy of cup positioning by inexperienced surgeons.

Clinical Outcome of Arthroscopic Partial Resection of Hip Acetabular Labrum Tear: A Case Report

51歳男性．1年程前より，誘因なく右股関節痛が出現し，平成18年10月当科紹介受診．股関節内外旋での疼痛認めるも，単純レントゲンにて明らかな異常を認めなかった．腰椎を含め，他部位に異常を認めず，臨床所見より股関節唇損傷を疑い，MRI，CT arthrographyを行った．その結果，いずれにおいても関節唇の一部に関節唇損傷を疑う所見を認めた．また，関節内局麻注入にて一時的な症状改善を認め，症状，画像を総合的に判断し，最終的に関節唇損傷と診断し，関節鏡を行った．鏡視にて前外側の関節唇損傷を認め，鏡視下関節唇切除術を行った．術後早期より，歩行時の疼痛などの症状の改善を認め，経過良好である．股関節唇損傷は症状やCT arthrography，MRI，関節内局麻注入などで診断されることが多いが，画像上明らかな異常所見がない例も少なくない．原因が明らかでない股関節痛が持続する症例では，関節唇損傷も考慮に入れて，関節鏡を用いた．診断治療を行うことは有効な方法であると考える．

Clinical Findings of Chiari Pelvic Osteotomy with Arthroscopic Debridement for Osteoarthritis of Hip

（目的）キアリ骨盤骨切り術施行時と内固定材料抜釘時に股関節鏡を行い，鏡視所見と治療成績について検討した．（対象と方法）2001年以降のキアリ症例44例47股中，鏡視を行い得た10例10股（全例女性）を対象とした．手術時平均年齢は43歳で，抜釘術までの期間：平均1年1ケ月，病期分類は進行期3例，末期7例であった．評価はJOAスコアと種田分類を用いた．（結果と考察）JOAスコアは48点から74点に改善していた．種田分類では多くの症例で変化なかった．疼痛などの臨床所見はよく改善されていたが，関節鏡所見の変化は乏しく，臨床成績との関連性は明らかではなかった．またキアリ変法に関節内処置を併用することが，どれほど臨床成績の向上に貢献しているかも不明であるため，今後長期にわたる経過観察が必要であると思われる．

Two Cases of Cervical Disc Hernia after Anterior Fusion

We successfully treated two patients with cervical disc hernia after anterior fusion. Case 1 was a 50-year-old woman. In 1991 she underwent anterior cervical fusion after being diagnosed with cervical disc hernia (CDH) at another hospital and postoperative course was good. Ten years later, due to numbness of both hands and finger elaborate movement disorder developed, and she visited our hospital for checkup. Cervical disc herinia was noted at the proximal adjacent level of the previous fusion level in magnetic resonance imaging (MRI), for which we performed anterior cervical fusion again. Postoperatively, numbness of the arms and elaborate movement disorder improved. Her Japan Orthopedic Association(JOA) score improved 16 points from 12 points.Case 2 was a 60-year-old man. In 1993 he underwent anterior cervical fusion after being diagnosed with CDH and ossification of the posterior longitudinal ligament. Eight years later, he visited our hospital again for checkup due to numbness of both arms and urine leak. We recognized CDH at the proximal adjacent level of the previous fusion level in MRI for which we performed front fusion again. Postoperatively, spastic paralysis improved. JOA score also improved 12 points from 10 points and he was able to return to work.

Analysis of the Questionnaire on the Sport Injury to High-school Baseball Pitchers.

Background: In this study, we attempted to determine the connection between throwing injuries, especially to the shoulder or elbow, and the amount of pitching practice, in high-school pitchers. Methods: We distributed questionnaires to 67 high-school baseball pitchers and had them answer questions on the following: their sports career, past sport-related injuries, the amount of baseball practice per day and per week, the number of throws per day, and the number of non-throwing day per week. Using an unpaired T-test, we looked for statistical relationships between throwing injuries and the above factors. Results: Of the 67 cases that answered our questionnaire, 53 (79.1%) answered that they had suffered sports-related injuries in their careers. Of these, 48 (71.6%) had suffered throwing injuries to the shoulder or elbow. Our examination showed that 34 pitchers (50.7%) currently had derangement of the shoulder or elbow, and the questionnaires showed that these pitchers had spent much more time practicing throwing in elementary school and junior high school than those without these problems. Conclusion: Excessive throwing practice in elementary school and junior high school may lead to derangement of the shoulder or elbow.