4-parvifuran inhibits metastatic and invasive actions through the JAK2/STAT3 pathway in osteosarcoma cells

윤형문,박경란,TRANHONG QUANG,오현철,홍진태,김윤철,김은철 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.5

This study was performed to examine the anticancerand anti-metastatic effects of 4-parvifuran (PVN), anovel flavonoid isolated from the heartwood of Dalbergiaodorifera, and to study its underlying signaling pathway inhuman osteosarcoma cells. In the present study, PVN wasfound to inhibit cell proliferation in a concentration- andtime-dependent manner in the human osteosarcoma celllines studied (MG-63 and U-2 OS) and induce apoptosis, asevidenced by Annexin V? and TUNEL? cells. Cleavedpoly (ADP-ribose) polymerase (PARP) and caspase-3 wereup-regulated while anti-apoptotic proteins including Bcl-2,Bcl-xL, and survivin were down-regulated after treatmentwith PVN. Matrigel cell migration assay, invasion assay,and soft agar assay were used to show that PVN effectivelysuppressed cell migration and invasion and colony formationin osteosarcoma cells. Protein and mRNA levels ofMMP-2 and MMP-9 were reduced by PVN in a concentration-dependent manner. Furthermore, PVN inhibitedJanus kinase 2 (JAK2)/signal transducers and activators oftranscription 3 (STAT3), mitogen-activated protein kinases(MAPKs) including JNK, ERK, p38 kinase, and cAMPresponse element-binding protein (CREB). Therefore, thisis the first study to demonstrate that PVN might be a novelanticancer and anti-metastatic agent for the treatment ofosteosarcoma through the inhibition of JAK2/STAT3,MAPKs, and CREB signaling pathways.

상완골 간부 골절 수술 후 발생한 요골신경 마비에서 시행한 초음파 검사 -증례 보고-

윤형문,고덕환,김형준,남경모,강대명,Yoon, Hyungmoon,Kho, Dukhwan,Kim, Hyeungjune,Nam, Kyoungmo,Kang, Daemyung 대한정형외과초음파학회 2012 대한정형외과 초음파학회지 Vol.5 No.2

상완골 간부 골절에 대한 수술적 치료 후 발생하는 요골신경 마비는 흔치 않다. 하지만 수술 후 요골신경 손상 정도를 정확히 진단하고 예후를 예측하기가 어려워 수술적 치료를 요할 수 있다. 저자들은 상완골 간부 골절에 관혈적 정복 및 금속판 내고정 수술 후 발생한 요골신경 마비에서 초음파 검사를 시행하여 신경의 연속성을 확인하였다. 이 후 보존적 치료를 시행하여 마비가 회복된 1예를 경험하여 문헌고찰과 함께 보고하는 바이다. Radial nerve palsy after surgery of humerus fracture is uncommon complication. Occasionally it needs operative treatment because of difficulty to accurate evaluation. We report this case of radial nerve palsy after surgery of humerus shaft fracture with ultrasound examination. We checked the continuity of radial nerve and radial nerve palsy was complete recovered with conservative treatment.

줄기 세포를 이용한 관절 연골 손상의 치료

윤형문 ( Hyung Moon Yoon ),김석중 ( Seok Jung Kim ),김태균 ( Tae Gyun Kim ) 대한류마티스학회 2012 대한류마티스학회지 Vol.19 No.3

The natural history after articular cartilage injury is unclear. However, it is generally accepted that once articular cartilage is injured, its ability to regenerate is limited and that injury progresses to arthritis with time. Over the years various treatments have been developed and are used, such as arthroscopic debridement, microfracture, multiple drilling, osteochondral transfer, and Autologous Chondrocyte Implantation (ACI). These can be divided into treatment methods which apply cells and those which apply tissue. The former include abrasion chondroplasty, microfracture, multiple drilling, and ACI. The latter include osteochondral transfer and allograft. Combination treatments using both cells and tissues are new-generation ACI and microfracture with biomaterials. The clinical applications of stem cell therapy is still at an early stage, but shows much promise, particularly in the management of cartilage defects.

골다공증 척추 골절에서 전방 감압술 및 기기 이용 전방 유합술

하기용,류승준,윤형문 대한척추외과학회 2003 대한척추외과학회지 Vol.10 No.3

Tectorigenin Promotes Osteoblast Differentiation and in vivo Bone Healing, but Suppresses Osteoclast Differentiation and in vivo Bone Resorption

이소연,김규태,윤형문,김윤철,권일근,김은철 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.5

Although tectorigenin (TG), a major compound in the rhizome of Belamcanda chinensis, is conventionally used for the treatment of inflammatory diseases, its effects on osteogenesis and osteoclastogenesis have not been reported. The objective of this study was to investigate the effects and possible underlying mechanism of TG on in vitro osteoblastic differentiation and in vivo bone formation, as well as in vitro osteoclast differentiation and in vivo bone resorption. TG promoted the osteogenic differentiation of primary osteoblasts and periodontal ligament cells. Moreover, TG upregulated the expression of the BMP2, BMP4, and Smad-4 genes, and enhanced the expression of Runx2 and Osterix. In vivo studies involving mouse calvarial bone defects with CT and histologic analysis revealed that TG significantly increased new bone formation. Furthermore, TG treatment inhibited osteoclast differentiation and the mRNA levels of osteoclast markers. In vivo studies of mice demonstrated that TG caused the marked attenuation of bone resorption. These results collectively demonstrated that TG stimulated osteogenic differentiation in vitro, increased in vivo bone regeneration, inhibited osteoclast differentiation in vitro, and suppressed inflammatory bone loss in vivo. These novel findings suggest that TG may be useful for bone regeneration and treatment of bone diseases.

상부 관절와 및 관절와 순의 해부학적 분석

최남용,송현석,윤형문,최승균,Choi, Nam-Yong,Song, Hyun-Seok,Yoon, Hyung-Moon,Choi, Seung-Gyun 대한관절경학회 2010 대한관절경학회지 Vol.14 No.2

목적: 상부 관절와에 부착하는 관절와 순에 발생한 병변에 대한 봉합술 후의 결과가 모든 예에서 만족스러운 것은 아니다. 본 저자들은 상부 관절와 순의 치료에 도움이 되는 해부학적인 정보를 얻고자 견관절 자기 공명 영상 검사를 분석하고, 상부 관절와 순이 부착하는 부위의 관절와의 해부학적인 형태 및 부착 양상을 알아보고자 하였다. 대상 및 방법: 본원에서 견관절 자기 공명 영상 검사를 시행한 108예에서 관상면 영상을 분석하였다. 평균 연령은 52세(17~71세)였으며, 남자는 55예였고 여자는 53예였다. 일반적으로 상부 관절와 순 파열에서 봉합하게 되는 영역인, 이두건 장두의 관절와 부착 부위의 후방 2개 영상에서 관절와 순의 부착 부위의 길이 및 상외측 관절와의 단면 각도를 측정하였다. 결과: 상부 관절와 순의 관절와 전방 부착 부위의 내-외측 길이는 평균 $9.78{\pm}1.64\;mm$였다. 남자는 평균 $10.1{\pm}1.61\;mm$, 여자는 평균 $9.43{\pm}1.6\;mm$였다. 상외측 관절와의 각도는 평균 $89.6{\pm}7.6$도였다. 결론: 관상면에서의 상부 관절와 순의 부착 부위는 후방이 전방보다 짧다. 상외측 관절와의 각도는 후방이 전방보다 작았다. Purpose: The results of the repair for the superior labrum lesions attaching at the superior glenoid have not been satisfactory in every cases. We wanted to analyze the shoulder MRI and the anatomical morphology and pattern of the superior glenoid at which the superior labrum attaches to get anatomical information helpful in treating the superior labrum. Materials and Methods: We analyzed the coronal images of the shoulder MRI of 108 cases taken at our hospital. Average age was 52 years (range, 17~71 years), 55 males and 53 females. On two coronal images behind the attachment of the long head of biceps that the repair of the SLAP was performed at, the length of the attachment of superior labrum and the angle of the supero-lateral glenoid were measured. Results: The average length of the attachment of superior labrum was $9.78{\pm}1.64\;mm$. The average length was $10.1{\pm}1.61mm$ in male, $9.43{\pm}1.6\;mm$ in female. The angle of the supero-lateral glenoid was $89.6{\pm}7.6$ degrees. Conclusion: The attachment of the superior labrum in coronal plane was shorter in posterior spot than anterior. The angle of the supero-lateral glenoid was less in posterior spot.

Clinical Article : 주관절의 외반 신전 과부하 증후군 야구선수에서 시행한 관절경하 주두 골극절제술

박진영 ( Jin Young Park ),윤형문 ( Hyung Moon Yoon ),오경수 ( Kyung Soo Oh ),유현열 ( Hyun Yul Yoo ),방진영 ( Jin Young Bang ),강대명 ( Dae Myung Kang ) 대한스포츠의학회 2013 대한스포츠의학회지 Vol.31 No.2

We evaluated the clinical outcome after arthroscopic olecranon osteophyte resection without ligament operation in the elite baseball players who had valgus extension overload syndrome without moderate or severe medial collateral ligament injury. From January 2007 to December 2011, twelve patients underwent arthroscopic osteophyte resection without ligament operation and they were followed for more than 12 months. The mean age was 19.2 years and mean follow-up period was 26 months. The clinical results were evaluated using range of motion, visual analogue scale (VAS) and Mayo elbow performance score (MEPS). After checking osteophyte size and location through 3-dimensional computed tomography, arthroscopic osteophyte resection was performed. Average preoperative extension, flexion, pronation and supination were 2.3o, 138.2o, 76.4o, and 69.1o. Average postoperative extension, flexion, pronation and supination had been changed into 0.7o, 137.3o, 79.1o, and 77.3o. Average preoperative pain VAS and MEPS were 5.5 and 67.5. Average postoperative pain VAS and MEPS had been changed into 0.4 (p <0.001) and 97.5 (p<0.001). Eleven patients returned to play. Ten cases returned to their own position. No patients were performed other operation for elbow pain. The arthroscopic osteophyte resection in valgus extension overload syndrome with low grade medial ulnar collateral ligament (MUCL) injury or without MUCL injury was a one of the ideal treatment option for early return to pre-injury levels and relief of pain.

주관절 강직의 병태 생리

송현석(Hyun Seok Song),윤형문(Hyung Moon Yoon) 대한견주관절의학회 2010 대한견주관절의학회지 Vol.13 No.2

목적: 관절의 적절한 기능을 위해서는 관절의 안정성과 운동 범위의 유지가 필요하다. 주관절과 연관된 환자의 주소의 대부분이 주관절의 강직이다. 최근 보고들에서 주관적의 강직에 대한 치료에서 우수한 결과가 보고되고 있다. 그러나 어떠한 술식을 선택하여야 하는 것은 결정하기 어렵다. 대상 및 방법: Morrey 등은 기능적인 운동 범위를 30-130도의 굴곡-신전 범위, 50도 회내전 및 50도 회외전이라고 하였다. 이 범위에서 일상 생활의 약 90%가 이루어 진다. 주관절 강직은 원인이 되는 외상과 주 병변의 위치에 따라서 분류할 수 있다. 관절 내 원인으로는 심각한 관절 내 불일치, 관절 내 유착 또는 관절 내 연골의 소실, 골극 형성에 의한 기계적 제한, 관절 내 유리체, 활액막의 과다 증식이 해당된다. 관절 외 원인으로는 외상 또는 탈구에 의한 심한 관절막의 유착, 측부 인대 또는 근육의 구축이 해당된다. 결과 및 결론: 신전 제한의 주 원인은 전방 관절막의 섬유화에 의한 구축이다. 이러한 병변은 전방 관절막 절제술이 도움이 된다. 굴곡 제한의 주 원인은 내측부 인대의 후방대의 구축이다. Purpose: Stability of joints and maintenance of range of motion are needed for optimum function. The most common complaint about the elbow joint is joint stiffness. Recent articles have reported good outcomes in the treatment of stiff elbow joints. However, deciding which procedure to use is always difficult. Materials and Methods: Morrey et al. reported that the functional range of motion of the elbow joint is 30-130° of flexion-extension and 50° of supination and pronation. About 90% of daily activities are done using this range of motion. Stiff elbow joints can be classified according to the traumatic events that caused the problem or the location of the main pathology. Intraarticular pathology includes severe articular mismatch, intraarticular adhesions, loss of articular cartilage, mechanical blockade by osteophytes, loose bodies, and hypertrophied synovium. Extraarticular pathology includes severe capsular adhesion due to the trauma or to dislocation, contracture of the collateral ligaments or muscles, bony bridge. Results and Conclusions: The main pathology underlying the loss of extension is the fibrous contracture of the anterior capsule. In this pathology, an anterior capsulectomy would be helpful. The main pathology underlying the loss of flexion is the contracture of the posterior band of medial collateral ligament.

RANKL-induced osteoclastogenesis is suppressed by 4-O-methylhonokiol in bone marrow-derived macrophages

박경란,김지연,김은철,윤형문,홍진태 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.8

Magnolol, honokiol, and obovatol are wellknown bioactive constituents of the bark of Magnoliaofficinalis and have been reported to have beneficial effectsin various diseases. We recently isolated a novel activecompound, 4-O-methylhonokiol (4-O-MH) from the ethanolextract of M. officinalis, which was previously reportedto have pharmacological effects including anti-inflammatory,anti-oxidative, and anti-aging activities. Here, weexamined the pharmacological properties of 4-O-MH onosteoblast (bone-forming cells) and osteoclast (bone-resorbingcells) differentiation, and its underlying signalingpathways in primary cultured pre-osteoblasts and bonemarrow macrophages. Our results showed that 4-O-MH didnot affect cell viability in pre-osteoblasts and did notinfluence osteoblast differentiation and mineralized noduleformation, as assessed by alkaline phosphatase activity andAlizarin red staining. However, 4-O-MH significantlyinhibited TRAP-positive multinuclear osteoclasts andF-actin ring formation during Receptor activator of NF-jBligand (RANKL)-mediated osteoclastogenesis withoutcytotoxicity. In addition, 4-O-MH suppressed RANKL-inducedcritical factors (c-Fos, NF-ATc1, TRAP, and ITB3)for osteoclast differentiation and function. Furthermore,RANKL-mediated signaling, including ERK1/2, AKT, andNF-kB pathways was attenuated by 4-O-MH. Takentogether, 4-O-MH has an inhibitory role in RANKL-mediatedosteoclastogenesis but not osteoblast differentiation,and our findings also suggest that 4-O-MH is a potentialtherapeutic agent for bone-destructive diseases such asosteoporosis, alveolar bone resorption, and osteoarthritis.

외반 신전 과부하 증후군 야구선수에서 주두 골극 제거술

박진영(Jin-Young Park),윤형문(Hyung-Moon Yoon),고덕환(Duk-Hwan Kho),오경수(Kyung-soo Oh),유현열(Hyun-Yul Yoo) 대한견주관절의학회 2013 대한견주관절학회 학술대회논문집 Vol.2013 No.3