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The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis.

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Frailty has been gathering attention as a factor to predict surgical outcomes. However, the association of frailty with postoperative complications remains controversial in spinal metastases surgery. We therefore designed a prospective study to elucidate risk factors for postoperative complications with a focus on frailty.

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To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis.

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Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear.

Coaxial autografts of skeletal muscle which had been frozen then thawed were used to repair injured digital nerves in eight patients. Assessment from three to 11 months after operation showed recovery to MRC sensory category S3+ in all but one patient, an excellent level of recovery. We conclude that bespoke muscle grafts treated and used in this way may offer significant advantages over conventional nerve grafts or cable grafts especially where large peripheral nerves are involved

A total of 38 patients with leprosy and localised nerve damage (11 median at the wrist and 37 posterior tibial at the ankle) were treated by 48 freeze-thawed skeletal muscle autografts ranging between 2.5 cm and 14 cm in length. Sensory recovery was noted in 34 patients (89%) and was maintained during a mean period of follow-up of 12.6 years (4 to 14). After grafting the median nerve all patients remained free of ulcers and blisters, ten demonstrated perception of texture and eight recognised weighted pins. In the posterior tibial nerve group, 24 of 30 repairs (80%) resulted in improved healing of the ulcers and 26 (87%) demonstrated discrimination of texture. Quality of life and hand and foot questionnaires showed improvement; the activities of daily living scores improved in six of seven after operations on the hand, and in 14 of 22 after procedures on the foot. Another benefit was subjective improvement in the opposite limb, probably because of the protective effect of better function in the operated side. This study demonstrates that nerve/muscle interposition grafting in leprosy results in consistent sensory recovery and high levels of patient satisfaction. Ten of 11 patients with hand operations and 22 of 25 with procedures to the foot showed sensory recovery in at least one modality

1. The effects of heavy training on a skeletal muscle have been studied in the rat. After denervation of the triceps surae muscle the tendon of the plantaris muscle was implanted into the tuberosity of the calcaneum. It was then possible to demand an unusual performance of the plantaris, the weight of which is only 18 per cent of the weight of the triceps surae. 2. Formation of new muscle fibres was observed after prolonged heavy training. This is incontrast to the opinion of most investigators, who have seen no new fibres formed after training. Degenerative changes followed by regeneration were also seen. 3. The trained muscle could almost double its weight, and treble its force. Paradoxically, the supposedly non-contractile sarcoplasm was seen to have increased after training. 4. Training induced a strong protein synthesis in muscle. In normal muscle protein synthesis can hardly be demonstrated. 5. Connective tissue grew between single muscle fibres in the heavily trained muscle. Its distribution was unequal. 6. Heavy exercise caused marked swelling of an untrained muscle. 7. Functional recovery was satisfactory after the operation. This showed that a muscle can be replaced by one only one-fifth its weight, provided the latter is trained adequately. 8. Not even the most arduous training could inflict permanent damage on the muscle

1. Direct injury to skeletal muscle results in fragmentation and necrosis of muscle fibres, though this is patchy in distribution. 2. The sarcolemmal basement membranes form the interface along which fibre regeneration takes place. 3. Phagocytosis of disorganised sarcoplasm is an essential prelude to the reconstitution of severely damaged fibres. 4. Regeneration of injured muscle begins with proliferation of basophilic cells probably originating from muscle satellite cells. After a few days typical myoblast nuclear chains are present. By a week following injury the chains of myoblasts have formed myotubes, which possess myofibrils and sarcomeres. 5. By twelve days in the monkey and by eighteen days in man the muscle fibre regenerative process shows many new fibres which have not reached a mature diameter. 6. Much collagen may be formed in the tissue space at the site of injury. It appears that as the muscle fibres increase in diameter the collagen decreases in extent. 7. In the monkey by three weeks the muscle at the fracture site appears normal. This is also true in the specimens examined at four, six and twelve weeks. 8. In the monkeys the injured limb was immediately used to run and jump. A parallel intense and early activity of muscle and joints was a cardinal point in the management of this series of fracture patients. The clinical results were satisfactory. 9. It is concluded that in both the monkey and in man, given active limb movements, permanent and functionally useful muscle regeneration occurs following soft-tissue injury associated with a bone fracture

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Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing.

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Dystrophic calcification (DC) is the abnormal appearance of calcified deposits in degenerating tissue, often associated with injury. Extensive DC can lead to heterotopic ossification (HO), a pathological condition of ectopic bone formation. The highest rate of HO was found in combat-related blast injuries, a polytrauma condition with severe muscle injury. It has been noted that the incidence of HO significantly increased in the residual limbs of combat-injured patients if the final amputation was performed within the zone of injury compared to that which was proximal to the zone of injury. While aggressive limb salvage strategies may maximize the function of the residual limb, they may increase the possibility of retaining non-viable muscle tissue inside the body. In this study, we hypothesized that residual dead muscle tissue at the zone of injury could promote HO formation.

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The gluteus minimus (GMin) and gluteus medius (GMed) have unique structural and functional segments that may be affected to varying degrees, by end-stage osteoarthritis (OA) and normal ageing. We used data from patients with end-stage OA and matched healthy controls to 1) quantify the atrophy of the GMin and GMed in the two groups and 2) describe the distinct patterns of the fatty infiltration in the different segments of the GMin and GMed in the two groups.

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Vertebrates have adapted to life on Earth and its constant gravitational field, which exerts load on the body and influences the structure and function of tissues. While the effects of microgravity on muscle and bone homeostasis are well described, with sarcopenia and osteoporosis observed in astronauts returning from space, the effects of shorter exposures to increased gravitational fields are less well characterized. We aimed to test how hypergravity affects early cartilage and skeletal development in a zebrafish model.

1. Arthrography demonstrates two types of injury to the capsule in acute anterior dislocations of the shoulder. 2. The first is a capsular rupture which does not appear to lead to recurrent dislocation of the shoulder unless there is concomitant humeral head damage. In this group healing is complete in ten days and it should be safe to start exercises early. 3. The second is associated with labral detachment from the glenoid and most heal with immobilisation for three weeks. Failure to heal leads to recurrent dislocation. It is not known whether immobilisation had any influence on healing of the lesion in these patients and this remains the subject of further investigation. 4. In recurrent anterior dislocation of the shoulder there is constant enlargement of the subscapular bursa, the outline of which becomes continuous with the inferior pouch. Axial arthrographs show either an absence of the glenoid labral outline or an enlarged entrance to the subscapular bursa. 5. Ruptures of the supraspinatus portion of the tendinous cuff were seen in five patients out of a total of twenty-seven acute dislocations, suggesting that this associated injury is more common than was previously believed. POSTERIOR DISLOCATIONS. 6. When the dislocation is voluntary there is marked elasticity of the capsule but the joint is only unstable in one direction when examined under anaesthesia. Both shoulders appear equally affected when examined radiologically under general anaesthesia even though the patient only has the ability to dislocate one. 7. All patients with voluntary dislocation had a curious voluntary muscle control and were able to contract the anterior and posterior parts of deltoid separately. Each dislocation was preceded by scapular movement. 8. No evidence of increased joint laxity was found in other joints in any of the patients. 9. In two patients with acute dislocations the defect of the humeral head was seen after the initial dislocation and in the third patient it occurred at the time of the second dislocation. In all three there was a spill of fluid beneath the subscapularis but no leakage into the axilla as occurred in anterior dislocation with capsular rupture. The capacity for healing appeared greater than in anterior dislocations with labral detachment; one patient treated in a sling had a better functional result than another treated with the shoulder in lateral rotation

Chondrocyte hypertrophy represents a crucial turning point during endochondral bone development. This process is tightly regulated by various factors, constituting a regulatory network that maintains normal bone development. Histone deacetylase 4 (HDAC4) is the most well-characterized member of the HDAC class IIa family and participates in different signalling networks during development in various tissues by promoting chromatin condensation and transcriptional repression. Studies have reported that HDAC4-null mice display premature ossification of developing bones due to ectopic and early-onset chondrocyte hypertrophy. Overexpression of HDAC4 in proliferating chondrocytes inhibits hypertrophy and ossification of developing bones, which suggests that HDAC4, as a negative regulator, is involved in the network regulating chondrocyte hypertrophy. Overall, HDAC4 plays a key role during bone development and disease. Thus, understanding the role of HDAC4 during chondrocyte hypertrophy and endochondral bone formation and its features regarding the structure, function, and regulation of this process will not only provide new insight into the mechanisms by which HDAC4 is involved in chondrocyte hypertrophy and endochondral bone development, but will also create a platform for developing a therapeutic strategy for related diseases.

Cite this article: Bone Joint Res. 2020;9(2):82–89.

The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice.

Cite this article: Bone Joint Res 2020;9(7):351–359.

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Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing.

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Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model.

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Malignancy and surgery are risk factors for venous thromboembolism (VTE). We undertook a systematic review of the literature concerning the prophylactic management of VTE in orthopaedic oncology patients.