Osteoarthritis (OA) is a common degenerative disease characterized by the destruction of articular cartilage and chronic inflammation of surrounding tissues. Matrix metalloproteinase-13 (MMP-13) is the primary MMP involved in cartilage degradation through its particular ability to cleave type II collagen. Hence, it is an attractive target for the treatment of OA. However, the detailed molecular mechanisms of OA initiation and progression remain elusive, and, currently, there are no interventions available to restore degraded cartilage. This review fully illustrates the involvement of MMP-13 in the initiation and progression of OA through the regulation of MMP-13 activity at the molecular and epigenetic levels, as well as the strategies that have been employed against MMP-13. The aim of this review is to identify MMP-13 as an attractive target for inhibitor development in the treatment of OA.

Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis

With the increasing incidence of cartilage-related diseases such as osteoarthritis (OA) and intervertebral disc degeneration (IDD), heavier financial and social burdens need to be faced. Unfortunately, there is no satisfactory clinical method to target the pathophysiology of cartilage-related diseases. Many gene expressions, signaling pathways, and biomechanical dysregulations were involved in cartilage development, degeneration, and regeneration. However, the underlying mechanism was not clearly understood. Recently, lots of long non-coding RNAs (lncRNAs) were identified in the biological processes, including cartilage development, degeneration, and regeneration. It is clear that lncRNAs were important in regulating gene expression and maintaining chondrocyte phenotypes and homeostasis. In this review, we summarize the recent researches studying lncRNAs’ expression and function in cartilage development, degeneration, and regeneration and illustrate the potential mechanism of how they act in the pathologic process. With continued efforts, regulating lncRNA expression in the cartilage regeneration may be a promising biological treatment approach.

/pdf/lncrnas-function-and-mechanism-in-cartilage-development-1wraoy59hb.pdf

lncRNAs: function and mechanism in cartilage development, degeneration, and regeneration

Osteoclasts derived from the monocyte/macrophage hematopoietic lineage regulate bone resorption, a process balanced by bone formation in the continual renewal of the skeletal system. As dysfunctions of these cells result in bone metabolic diseases such as osteoporosis and osteopetrosis, the exploration of the mechanisms regulating their differentiation is a priority. A potential mechanism may involve long noncoding RNAs (lncRNAs), which are known to regulate various cell biology activities, including proliferation, differentiation, and apoptosis. The expression of the lncRNA AK077216 (Lnc-AK077216) is significantly upregulated during osteoclastogenesis identified by microarray and verified by qPCR. Up- and downregulation of Lnc-AK077216, respectively promotes and inhibits osteoclast differentiation, bone resorption, and the expression of related genes on the basis of tartrate-resistant acid phosphatase staining, qPCR, and western blot results. In addition, Lnc-AK077216 suppresses NIP45 expression and promotes the expression of NFATc1, an essential transcription factor during osteoclastogenesis. Besides, it was found that the expression of Lnc-AK077216 and Nfatc1 is upregulated, whereas Nip45 expression is downregulated in bone marrow and spleen tissues of ovariectomized mice. The results suggest that Lnc-AK077216 regulates NFATc1 expression and promotes osteoclast formation and function, providing a novel mechanism of osteoclastogenesis and a potential biomarker or a new drug target for osteoporosis.

LncRNA AK077216 promotes RANKL-induced osteoclastogenesis and bone resorption via NFATc1 by inhibition of NIP45.

https://eprints.ncl.ac.uk/file_store/production/254138/52B1EA0D-9E05-4F67-9691-BDD67449254B.pdf

Identification of long non-coding RNAs expressed in knee and hip osteoarthritic cartilage.

This study is applied to the investigation of the long noncoding RNA myocardial infarction associated transcript's (MIAT's) role in regulating the expression of high-mobility group box 1 (HMGB1) in cerebral microvascular endothelial cell (CMEC) injury after cerebral ischemia by serving as a competitive endogenous RNA (ceRNA) to sponge microRNA-204-5p (miR-204-5p). The cerebral ischemia model of middle cerebral artery occlusion (MCAO) in rats was established by the suture method, in which rats were injected with empty plasmids and MIAT siRNA plasmids. The cerebral ischemia injury model in vitro was established through oxygen glucose deprivation (OGD) in primary cultured CMECs in rats. The cells were transfected with empty plasmids and MIAT siRNA plasmids. The MIAT/miR-204-5p/HMGB1 axis' function in damage and angiogenesis of CMECs were explored. The binding site between MIAT and miR-204-5p along with that between miR-204-5p and HMGB1 was determined. MIAT was overexpressed in MCAO rats' brain tissue and inhibited MIAT attenuated the injury of brain tissue in MCAO rats. Inhibition of MIAT promoted angiogenesis, promoted miR-204-5p expression and inhibited HMGB1 expression in brain tissue of MCAO rats. Inhibition of MIAT reduced CMEC damage, induced angiogenesis of CMECs, increased the number of surviving neurons, promoted miR-204-5p expression and inhibited HMGB1 expression in CMECs treated with OGD. MIAT promoted HMGB1 expression by competitive binding to miR-204-5p to regulate the injury of CMECs after cerebral ischemia. Our study showed that MIAT promoted HMGB1 expression by competitively binding to miR-204-5p to regulate the injury of CMECs after cerebral ischemia.

Long noncoding MIAT acting as a ceRNA to sponge microRNA-204-5p to participate in cerebral microvascular endothelial cell injury after cerebral ischemia through regulating HMGB1.

// Guodong Wang 1, * , Xianmin Bu 2, * , Yuanmin Zhang 1, * , Xiaowei Zhao 1 , Ying Kong 1 , Longfei Ma 1 , Shuaishuai Niu 1 , Bin Wu 1 and Chunyang Meng 1 1 Department of Orthopaedics, Affiliated Hospital of Jining Medical University, Jining, Shandong, China 2 Department of Pathology, Shandong Jining No.1 People's Hospital, Jining, Shandong, China * These authors contributed equally to this work Correspondence to: Chunyang Meng, email: frvr11@yeah.net Keywords: osteoarthritis, long noncoding RNAs, UCA1, miR-204-5p, MMP-13 Received: June 02, 2017      Accepted: July 25, 2017      Published: August 10, 2017 ABSTRACT Osteoarthritis (OA) is a common degenerative disease characterized by degeneration of articular cartilage. Increasing studies showed that long noncoding RNAs (lncRNAs) play important roles in the cartilage damage. However, little is known about the role of UCA1 in the osteoarthritis. The expression level of UCA1 was upregulated in the OA cartilage. Overexpression of UCA1 suppressed the miR-204-5p expression in the chondrocytes. The expression of miR-204-5p was downregulated in the OA cartilage. Moreover, the expression of miR-204-5p was negatively correlated with the UCA1 expression in the OA cartilage. Elevated expression of UCA1 promoted the chondrocytes cell proliferation and overexpression of miR-204-5p suppressed chondrocytes cell proliferation. In addition, overexpression of UCA1 decreased the expression of the type II collagen and type IV collagen expression in the chondrocytes. Elevated expression of miR-204-5p promoted the type II collagen and type IV collagen expression in the chondrocytes. We idetified MMP-13 was a direct target gene of miR-204-5p in the chondrocytes. Overexpression of UCA1 enhanced the MMP-13 expression in the chondrocytes. Elevated expression of UCA1 regulated the chondrocytes cell proliferation and collagen expression through inhibiting the miR-204-5p expression.These results suggested that UCA1 played as an important regulator of survival and matrix synthesis of chondrocytes partly through suppressing the miR-204-5p expression.

/pdf/lncrna-uca1-enhances-mmp-13-expression-by-inhibiting-mir-204-4if8qzkjre.pdf

LncRNA-UCA1 enhances MMP-13 expression by inhibiting miR-204-5p in human chondrocytes.

To investigate the efficacy of the minimally invasive clamp reduction technique via the anterior approach in the treatment of irreducible intertrochanteric femoral fractures.From January 2015 to January 2021, 115 patients (48 males and 67 females) with irreducible intertrochanteric femoral fractures were treated. The average age of the patients was 78.7 (45-100 years old). The types of injuries were falls (91 cases), traffic accidents (12 cases), smashing (6 cases), and high falling (6 cases). The duration between injury and surgery ranged from 1 to 14 days, with an average of 3.9 days. The distribution of AO classification was as follows: 31-A1 in 15 cases, type 31-A2 in 67 cases and 31-A3 in 33 cases.All patients achieved good reduction, with fracture reduction times ranging from 10 to 32 min (mean of 18 min), and were followed up for 12-27 months after surgery (mean of 17.9 months). Two patients with pronation displacement of the proximal fracture segment died of infection or hypostatic pneumonia after internal fixation failure; one patient with failed internal fixation switched to joint replacement. After internal fixation, the lateral wall of six reversed intertrochanteric femoral fractures showed repronation and abduction displacement, but all fractures achieved bony healing. The rest of the patients did not lose fracture reduction, and all fractures achieved bony healing with a healing time ranging from 3 to 9 months (mean of 5.7 months). While two patients died and one patient exhibited failed internal fixation and thus switched to joint replacement, 91 of the remaining 112 patients had an excellent Harris score of the hip joint function at the final follow-up, while 21 patients had a good Harris score.The minimally invasive clamp reduction technique via the anterior approach for the treatment of irreducible intertrochanteric femoral fractures is simple, effective and minimally invasive. In the case of irreducible intertrochanteric femoral fractures associated with lateral wall displacement, the lateral wall needs to be strengthened after clamp reduction and intramedullary nail fixation to avoid loss of reduction and failure of internal fixation. 

/pdf/treatment-of-irreducible-intertrochanteric-femoral-fracture-3s6bfwlv.pdf

Treatment of irreducible intertrochanteric femoral fracture with a minimally invasive clamp reduction technique via the anterior approach

Comparative Study of Trans-Axillary Approach and Delto-Pectoral Approach to the Treatment of Ideberg Types I and II Scapular Glenoid Fractures.

OBJECTIVE
Ankle joint fractures are often accompanied by medial deltoid ligament rupture. There is controversy over whether or how to treat deltoid ligament rupture. This study was aimed to explore the feasibility of repairing the medial deltoid ligament using Kirschner wire internal fixation of the medial tibiotalar joint combined with external fixation.


METHODS
Forty-six patients with ankle fractures involving deltoid ligament rupture, treated between October 2012 and February 2021, were retrospectively evaluated. Twenty-five patients were treated with a Kirschner wire to fix the tibiotalar joint and indirectly repair the deltoid ligament as the repaired group. Twenty-one patients underwent reduction and fixation of internal and external malleolus fractures, and the deltoid ligament was not repaired in the unrepaired group. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, visual analog scale (VAS), Medical Outcomes Short Form 36-item questionnaire score (SF-36), and Medial clear space perpendicular (preoperative, postoperative, final follow-up) were used for functional evaluations and reduction assessments. Mann-Whitney test were used to compare the differences between the groups.


RESULTS
The follow-up time was 13-112 months with a mean of 59.32 months for the repaired group and 11-94 months with a mean of 53.43 months for the unrepaired group. There was no significant difference in the operative time or intraoperative blood loss between the two groups (p > 0.05). At the last follow-up, the AOFAS ankle-hindfoot and SF-36 scores of the repaired group were significantly higher than those of the non-repaired group (p < 0.05). Moreover, the VAS pain score was significantly lower and the Medial clear space perpendicular was significantly narrower in the repaired group than that in the unrepaired group.


CONCLUSION
Tibiotalar joint fixation using Kirschner wires is a simple and effective technique that can indirectly reduce and repair the deltoid ligament and stabilize the ankle.

Kirschner Wire Internal Fixation of the Medial Tibiotalar Joint for Indirect Repair of Deltoid Ligament Injury: A Retrospective Comparative Study.

Effects of 1-stage revascularization and temporary external fixation combined with 2-stage Ilizarov technique in the treatment of bone defects in lower limb destruction injury: A case report

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