Injury to muscles is very common. We have previously observed that basic fibroblast growth factor (b-FGF), insulin growth factor type 1 (IGF-1) and nerve growth factor (NGF) are potent stimulators of the proliferation and fusion of myoblasts in vitro. We therefore injected these growth factors into mice with lacerations of the gastrocnemius muscle. The muscle regeneration was evaluated at one week by histological staining and quantitative histology. Muscle healing was assessed histologically and the contractile properties were measured one month after injury. Our findings showed that b-FGF, IGF and to a less extent NGF enhanced muscle regeneration in vivo compared with control muscle. At one month, muscles treated with IGF-1 and b-FGF showed improved healing and significantly increased fast-twitch and tetanus strengths. Our results suggest that b-FGF and IGF-1 stimulated muscle healing and may have a considerable effect on the treatment of muscle injuries

Experimentally produced fractures in long bones studied by light and electron microscopic histochemistry were found to heal by a process of enchondral calcification. There was intense proliferation in the cells of the cambium layer of the periosteum, with differentiation to chondroblasts and osteoblasts, suggesting that this layer was the primary tissue responsible for development of the callus. Cytoplasmic processes of the hypertrophic chondrocytes appeared to bud and produce matrix vesicles. Alkaline phosphatase activity was detected along the plasma membrane of the hypertrophic chondrocytes and around the matrix vesicles, before any signs of mineral deposition. Calcification took place by deposition of hydroxyapatite crystals in and around these matrix vesicles which frequently showed alkaline phosphatase activity. It is suggested that there is a close functional association between alkaline phosphatase activity and calcification in the process of fracture healing, which is another type of enchondral calcification mediated by matrix vesicles

The acute childhood diseases haematogenous staphylococcal osteomyelitis and septic arthritis were studied concurrently using avian models which closely resemble the human diseases. Ultrastructural studies during the initial stages of bone and joint infection showed that adherence of bacteria to cartilage, bacterial proliferation, cartilage destruction and subsequent bacterial spread along the vascular channels within cartilage were common to both disease processes. Histological studies revealed that transphyseal blood vessels were present in the growing chickens and were a likely explanation for the frequency of the concurrence of acute osteomyelitis and adjacent joint infection following intravenous injection of bacteria. Transphyseal vessels provide a direct connection between the growth plate (physis) and epiphyseal cartilage supplying a route for bacteria to spread from an osteomyelitic focus in the metaphysis to the epiphysis and subsequently to the joint lumen

Unlike hyaline cartilage, mandibular condylar cartilage can respond to injury by complete healing. We have used the reparative potential of mandibular cartilage to promote repair of defects in a hyaline cartilage joint surface. In 12 adult marmosets, articular fibrocartilage from the mandibular condyles was transplanted into full-thickness defects created in the femoral condyles. Additional defects acted as an ungrafted control group. The grafted defects showed good incorporation of the transplant with restoration of the articular surface within six months. Repair was by proliferation of the fibrocartilaginous graft and chondrogenesis of hyaline cartilage. The repopulating cells were distributed in a matrix of maturing collagen and sulphated glycosaminoglycans. Ungrafted control defects were only partly repaired with fibrous tissue, leaving articular deficiencies. We conclude that transplanted mandibular fibrocartilage can promote reconstitution of wounded hyaline cartilage joint surfaces in primates

The fine structure of palmar fascia from patients with Dupuytren's contracture (DC) was compared with that from patients with carpal tunnel syndrome (CTS). In contrast to previous assumptions, the ultrastructure of fibroblasts both in vivo and in vitro from DC and CTS appeared identical, indicating that myofibroblasts are not specific to DC. The major differences between DC and CTS were: 1) a sixfold and fortyfold increase in fibroblast density in cord and nodular areas of DC compared with CTS; 2) a more disorganised pattern of collagen fibrils in DC; and 3) markedly narrowed microvessels surrounded by thickened, laminated basal laminae and proliferating fibroblasts in DC compared with CTS. To account for these morphological changes a hypothesis is presented which proposes that oxygen-free radicals cause pericytic necrosis and fibroblastic proliferation. This hypothesis provides a potential avenue for therapy of DC and other fibrotic conditions

The release of prostaglandins E and F from the tibiae of rabbits and the surrounding muscle in vitro after fracture and pinning, or pinning alone, has been compared to the release from unoperated tissues. The fractured tibiae released significantly more prostaglandins E and F than the control tibiae three to 14 days after operation. The pinned tibiae also released more of the two prostaglandins, although this was significant only after 14 days. Consequently it was only around the third day that the fractured tibiae released significantly more prostaglandin E than the tibiae which had been pinned, but not fractured. Similar results were obtained for the release from the muscles surrounding the tibiae. Prostaglandins are important mediators of inflammation as well as potent stimulators of bone resorption. Their increased formation in response to fracture and pinning may stimulate the vascular changes, bone resorption and the proliferation of osteogenic cells observed after trauma to bone

1. Experiments are described in which total infarction of the epiphysis was produced in the metatarsal bones of growing rabbits. 2. After operation both proliferation and normal maturation of the cells of the growth plate were slowed or stopped. Cartilage destruction on the metaphysial side of the growth cartilage continued with consequent thinning of the cartilage. Localised areas of cell death appeared in the growth cartilage as early as the second day after operation. These increased in size and led to revascularisation of the epiphysis by metaphysial vessels which grew through the growth cartilage, reaching the epiphysis seven days after operation. The main, central part of the growth cartilage survived intact and its normal structure was restored after epiphysial revascularisation took place. Vessels growing into the bone from outside also contributed to revascularisation of the epiphysis. After revascularisation occurred, new bone formation led to increased radiographic density of the epiphysis

We evaluated histologically samples of synovial tissue from the knees of 50 patients with rheumatoid arthritis (RA). The samples were taken during revision for aseptic loosening. The findings were compared with those in 64 knees with osteoarthritis (OA) and aseptic loosening and in 18 knees with RA without loosening. The last group had been revised because of failure of the inlay or the coupling system of a constrained prosthesis. All the patients had had a total ventral synovectomy before implantation of the primary prosthesis. In all three groups a foreign-body reaction and lymphocellular infiltration were seen in more than 80% of the tissue samples. Deposits of fibrin were observed in about one-third to one-half of the knees in all groups. Typical signs of the reactivation of RA such as rheumatoid necrosis and/or proliferation of synovial stromal cells were found in 26% of knees with RA and loosening, but not in those with OA and loosening and in those with RA without loosening. Our findings show that reactivation of rheumatoid synovitis occurs after total knee replacement and may be a cofactor in aseptic loosening in patients with RA

Of 935 consecutive patients referred with shoulder pain, 50 fitted the criteria for primary frozen shoulder. Twelve patients who failed to improve after conservative treatment and manipulation had excision of the coracohumeral ligament and the rotator interval of the capsule. The specimens were examined histologically, using special stains for collagen. Immunocytochemistry was performed with monoclonal antibodies against leucocyte common antigen (LCA, CD45) and a macrophage/synovial antigen (PGMI, CD68) to assess the inflammatory component, and vimentin and smooth-muscle actin to evaluate fibroblasts and myofibroblasts. Our histological and immunocytochemical findings show that the pathological process is active fibroblastic proliferation, accompanied by some transformation to a smooth muscle phenotype (myofibroblasts). The fibroblasts lay down collagen which appears as a thick nodular band or fleshy mass. These appearances are very similar to those in Dupuytren's disease of the hand, with no inflammation and no synovial involvement. The contracture acts as a check-rein against external rotation, causing loss of both active and passive movement

In dogs, resection of a length of the ulna equal to twice the diameter of the mid-shaft leaves a defect which consistently fails to unite. In response to an implant of 100 mg of bovine bone morphogenetic protein (BMP), the defect becomes filled by callus consisting of fibrocartilage, cartilage and woven bone within four weeks. The cartilage is resorbed and replaced by new bone in four to eight weeks. Woven bone is then resorbed, colonised by bone marrow cells and remodelled into lamellar bone. Union of the defect is produced by 12 weeks. Control defects filled with autogeneic cortical bone chips unite after the same period. In regeneration induced by bone morphogenetic protein (BMP) and in repair enhanced by bone graft, union depends upon the proliferation of cells within and around the bone ends. Our working hypothesis is that BMP induces the differentiation of perivascular connective tissue cells into chondroblasts and osteoprogenitor cells and thereby augments the process of bone regeneration from the cells already present in the endosteum and periosteum

Aims

Tibiotalocalcaneal (TTC) fusion is used to treat a variety of conditions affecting the ankle and subtalar joint, including osteoarthritis (OA), Charcot arthropathy, avascular necrosis (AVN) of the talus, failed total ankle arthroplasty, and severe deformity. The prevalence of postoperative complications remains high due to the complexity of hindfoot disease seen in these patients. The aim of this study was to analyze the relationship between preoperative conditions and postoperative complications in order to predict the outcome following primary TTC fusion.

This paper describes a study in the human femur of the relationship between cell division in growth cartilage and overall bone growth. Growth rates for the distal femur from birth to eighteen years were determined from serial radiographs available from the Harpenden Growth Study; An average of 1-4 cm/year was found for the ages of five to eight years. The development of the growth plate is illustrated in a series of photomicrographs of femur sections. These sections were also used for quantitative histology; The length of the proliferation zone was estimated from cell counts to be twenty-four cells per column. On the basis of this value and the measured growth rate, an approximate mean cycle time of twenty days was found for the proliferating cells of the human growth plate. Since the corresponding cycle time is two days for rodent growth plates, which also have a different structure, it is unwise to extrapolate the findings in this tissue from mouse to man

1. Diametric growth and organisation of the epiphysial cartilage plate have been studied by microradiography of human bone and autoradiography of the epiphysial plate in growing rabbits, using sulphur. 35. These investigations were supplemented by a radiographic study of four patients with dyschondroplasia in whom the progress of the characteristic epiphysial defects were traced during several years' growth. 2. A perichondrial sheath of bone, at the junction of the epiphysial plate with the metaphysis, was demonstrated by microradiography of the distal end of the human femur. Its relationship to epiphysial growth is discussed. 3. Autoradiography, to determine the direction of the cellular proliferation between the epiphysial plate and the overlying perichondrium, demonstrated the appearance of new cartilage cells at the periphery of the plate over a period of six days. 4. The evidence presented strongly favours the postulate that the transverse diameter of the epiphysial cartilage plate increases by appositional growth from the overlying perichondrium and that the same source is responsible for lateral extension of the articular cartilage during growth

1. Radiographs of both shoulders were performed on 106 unselected necropsy subjects and those found to be abnormal were examined pathologically. 2. Radiological abnormalities were found in sixty-eight shoulders of thirty-eight subjects. Pathological examination showed rotator cuff tears and associated abnormalities in thirty-five of these, rheumatoid arthritis in one, a previous fracture in one, and one was not examined. 3. The criteria for radiological diagnosis of rotator cuff tears are examined and discussed. 4. The radiological changes give little indication of the severity of the tears or associated abnormalities except in the case of complete rupture of the cuff when acromio-humeral articulation occurs. 5. The lesions are all explicable on a traumatic basis. There is no correlation with the presence or absence of osteoarthritic disease of the joint. 6. The biceps tendon may become damaged or even ruptured in this condition. 7. Villous synovial proliferation was found in fourteen cases, in five of which it was pigmented with histological appearances resembling pigmented villonodular synovitis. The significance of this finding is briefly discussed

Aims

Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with limited coding potential, which have emerged as novel regulators in many biological and pathological processes, including growth, development, and oncogenesis. Accumulating evidence suggests that lncRNAs have a special role in the osteogenic differentiation of various types of cell, including stem cells from different sources such as embryo, bone marrow, adipose tissue and periodontal ligaments, and induced pluripotent stem cells. Involved in complex mechanisms, lncRNAs regulate osteogenic markers and key regulators and pathways in osteogenic differentiation. In this review, we provide insights into the functions and molecular mechanisms of lncRNAs in osteogenesis and highlight their emerging roles and clinical value in regenerative medicine and osteogenesis-related diseases.

Cite this article: J. Zhang, X. Hao, M. Yin, T. Xu, F. Guo. Long non-coding RNA in osteogenesis: A new world to be explored. Bone Joint Res 2019;8:73–80. DOI: 10.1302/2046-3758.82.BJR-2018-0074.R1.

The clinical, radiographic and pathological features of eighty-eight cases of histologically verified intra-osseous ganglia in eighty-three patients are described. All were located in the subchondral bone adjacent to a joint and most frequently involved the hip, the ankle (medial malleolus), the knee and the carpal bones. Forty-seven of the eighty-three patients were male and all the patients were between fourteen and seventy-three years of age, with an average age of forty-one years. There are two fundamental types of intra-osseous ganglia, one apparently arising by penetration of juxta-osseous ganglion into the underlying bone, a mechanism proved in fourteen of our eighty-eight cases (16 per cent); in the remaining seventy-four cases, the ganglion cyst was primarily intra-osseous ("idiopathic"). The initial cause of the intramedullary mucoid degeneration is discussed. We believe that mechanical stress and repeated minor trauma near the surface of the bone may lead to intramedullary vascular disturbance with consequent foci of aseptic bone necrosis. The revitalisation of these areas causes fibroblastic proliferation, followed by mucoid degeneration of the connective tissue, possibly due to some unknown local factor. Curettage or excision is usually effective, and recurrence (only four cases) is exceptional

We used an experimental rabbit model of leg lengthening to study the morphology and function of muscle after different distraction rates. Lengthening was in twice-daily increments from 0.4 to 4 mm per day. New contractile tissue formed during lengthening, but some damage to the muscle fibres was seen even at rates of less than 1 mm per day; abnormalities increased with larger rates of lengthening. There was proliferation of fibrous tissue between the muscle fibres at distraction rates of over 1 mm per day. Active muscle function showed adaptation when the rate was 1.0 mm per day or less, but muscle compliance was normal only after rates of 0.4 mm per day. Muscle responded more favourably at rates of distraction slower than those shown to lead to the most prolific bone formation. At present the rate of distraction in clinical practice is determined mainly by factors which enhance osteogenesis. Our study suggests that it may be advisable to use a slower rate of elongation in patients with poor muscle compliance associated with the underlying pathology; this will allow better accommodation by the contractile and connective tissues of the muscles

Cell therapies hold significant promise for the treatment of injured or diseased musculoskeletal tissues. However, despite advances in research, there is growing concern about the increasing number of clinical centres around the world that are making unwarranted claims or are performing risky biological procedures. Such providers have been known to recommend, prescribe, or deliver so called ‘stem cell’ preparations without sufficient data to support their true content and efficacy. In this annotation, we outline the current environment of stem cell-based treatments and the strategies of marketing directly to consumers. We also outline the difficulties in the regulation of these clinics and make recommendations for best practice and the identification and reporting of illegitimate providers.

Cite this article: Bone Joint J 2020;102-B(2):148–154