Identification of functional programmable mechanical stimulation (PMS) on tendon not only provides the insight of the tendon homeostasis under physical/pathological condition, but also guides a better engineering strategy for tendon regeneration. The aims of the study are to design a bioreactor system with PMS to mimic the in vivo loading conditions, and to define the impact of different cyclic tensile strain on tendon. Rabbit Achilles tendons were loaded in the bioreactor with/without cyclic tensile loading (0.25 Hz for 8 h/day, 0-9% for 6 days). Tendons without loading lost its structure integrity as evidenced by disorientated collagen fiber, increased type III collagen expression, and increased cell apoptosis. Tendons with 3% of cyclic tensile loading had moderate matrix deterioration and elevated expression levels of MMP-1, 3, and 12, whilst exceeded loading regime of 9% caused massive rupture of collagen bundle. However, 6% of cyclic tensile strain was able to maintain the structural integrity and cellular function. Our data indicated that an optimal PMS is required to maintain the tendon homeostasis and there is only a narrow range of tensile strain that can induce the anabolic action. The clinical impact of this study is that optimized eccentric training program is needed to achieve maximum beneficial effects on chronic tendinopathy management.

IntroductionAvascular necrosis of femoral head (ANFH) is a progressive disease that often leads to hip joint dysfunction and even disability in young patients. Although the standard treatment, which is core decompression, has the advantage of minimal invasion, the efficacy is variable. Recent studies have shown that implantation of bone marrow containing osteogenic precursors into necrotic lesion of ANFH may be promising for the treatment of ANFH.MethodsA prospective, double-blinded, randomized controlled trial was conducted to examine the effect of bone-marrow buffy coat (BBC) grafting combined with core decompression for the treatment of ANFH. Forty-five patients (53 hips) with Ficat stage I to III ANFH were recruited. The hips were allocated to the control group (core decompression + autologous bone graft) or treatment group (core decompression + autologous bone graft with BBC). Both patients and assessors were blinded to the treatment options. The clinical symptoms and disease progression were assessed as the primary and secondary outcomes.ResultsAt the final follow-up (24 months), there was a significant relief in pain (P <0.05) and clinical joint symptoms as measured by the Lequesne index (P <0.05) and Western Ontario and McMaster Universities Arthritis Index (P <0.05) in the treatment group. In addition, 33.3% of the hips in the control group have deteriorated to the next stage after 24 months post-procedure, whereas only 8% in the treatment group had further deterioration (P <0.05). More importantly, the non-progression rates for stage I/II hips were 100% in the treatment group and 66.7% in the control group.ConclusionImplantation of the autologous BBC grafting combined with core decompression is effective to prevent further progression for the early stages of ANFH.Trial registrationClinicalTrials.gov identifier NCT01613612. Registered 13 December 2011.

Tendons are the connective tissue responsible for transferring force from muscles to bones. A key factor in tendon development, maturation, repair, and degradation is its biomechanical environment. Understanding tendon mechanobiology is essential for the development of injury prevention strategies, rehabilitation protocols and potentially novel treatments in tendon injury and degeneration. Despite the simple overall loading on tendon tissue, cells within the tissue in vivo experience a much more complex mechanical environment including tension, compression and shear forces. This creates a substantial challenge in the establishment of in vitro loading models of the tendon. This article reviews multiple loading models used for the study of tendon mechanobiology and summarizes the main findings. Although impressive progress has been achieved in the functionality and mimicry of in vitro loading models, an ideal platform is yet to be developed. Multidisciplinary approaches and collaborations will be the key to unveiling the tendon mechanobiology. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:566-575, 2018.

The selection of a suitable scaffold matrix is critical for cell-based bone tissue engineering. This study aimed to identify and characterize natural marine sponges as potential bioscaffolds for osteogenesis. Callyspongiidae marine sponge samples were collected from the Fremantle coast of Western Australia. The sponge structure was assessed using scanning electron microscopy (SEM) and Hematoxylin and eosin. Mouse primary osteoblasts were seeded onto the sponge scaffold and immunostained with F-actin to assess cell attachment and aggregation. Alkaline phosphatase expression, von Kossa staining and real-time PCR were performed to examine the osteogenic potential of sponge samples. SEM revealed that the sponge skeleton possessed a collagenous fibrous network consisting of interconnecting channels and a porous structure that support cellular adhesion, aggregation and growth. The average pore size of the sponge skeleton was measured 100 to 300 μm in diameter. F-actin staining demonstrated that osteoblasts were able to anchor onto the surface of collagen fibres. Alkaline phosphatase expression, a marker of early osteoblast differentiation, was evident at 7 days although expression decreased steadily with long term culture. Using von Kossa staining, mineralisation nodules were evident after 21 days. Gene expression of osteoblast markers, osteocalcin and osteopontin, was also observed at 7, 14 and 21 days of culture. Together, these results suggest that the natural marine sponge is promising as a new scaffold for use in bone tissue engineering.

Many studies indicate that lead (Pb) and cadmium (Cd) exposure may alter bone development through both direct and indirect mechanisms, increasing the risk of osteoporosis later in life. The aim of this study was to investigate the association between Pb and Cd exposure, physical growth, and bone and calcium metabolism in children of an electronic waste (e-waste) processing area. We recruited 246 children (3-8 years) in a kindergarten located in Guiyu, China. Blood lead levels (BLLs) and blood cadmium levels (BCLs) of recruited children were measured as biomarkers for exposure. Serum calcium, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline were used as biomarkers for bone and calcium metabolism. Physical indexes such as height, weight, and head and chest circumference were also measured. The mean values of BLLs and BCLs obtained were 7.30 μg/dL and 0.69 μg/L, respectively. The average of BCLs increased with age. In multiple linear regression analysis, BLLs were negatively correlated with both height and weight, and positively correlated with bone resorption biomarkers. Neither bone nor calcium metabolic biomarkers showed significant correlation with cadmium. Childhood lead exposure affected both physical development and increased bone resorption of children in Guiyu. Primitive e-waste recycling may threaten the health of children with elevated BLL which may eventually cause adult osteoporosis.

Physiotherapy is one of the effective treatments for tendinopathy, whereby symptoms are relieved by changing the biomechanical environment of the pathological tendon. However, the underlying mechanism remains unclear. In this study, we first established a model of progressive tendinopathy-like degeneration in the rabbit Achilles. Following ex vivo loading deprivation culture in a bioreactor system for 6 and 12 days, tendons exhibited progressive degenerative changes, abnormal collagen type III production, increased cell apoptosis, and weakened mechanical properties. When intervention was applied at day 7 for another 6 days by using cyclic tensile mechanical stimulation (6% strain, 0.25 Hz, 8 h/day) in a bioreactor, the pathological changes and mechanical properties were almost restored to levels seen in healthy tendon. Our results indicated that a proper biomechanical environment was able to rescue early-stage pathological changes by increased collagen type I production, decreased collagen degradation and cell apoptosis. The ex vivo model developed in this study allows systematic study on the effect of mechanical stimulation on tendon biology. Keywords: bioreactor; degeneration; ex vivo; tendon; mechanical stimulationTendons are force-transmitting tissues connecting muscle to bone, which have the ability to sense and respond to different mechanical loading. [1][2][3][4][5] Because of this physiological function, biomechanics play an essential role in maintaining tendon homeostasis. [2][3][4][5] Normal healthy tenocytes are long spindle-shaped cells that bind to extracellular matrix proteins including collagen. 6 When tendon is subjected to physiological loading in vivo, the deformation of the cytoskeleton and cellular membrane attached to the collagen fibers can be sensed by cells, which initiate signaling cascades. 6-9 Accumulated evidence shows that in order to maintain normal tendon homeostasis, mechanical stimulation is required. 10-14 Yang et al. have reported that mechanical stretching can modulate proliferation of human tendon fibroblasts in the absence of serum and increase the cellular production of collagen type I, which is at least in part mediated via TGF-b. 15 Zeichen et al. reported that mechanical stress promotes tendon fibroblasts proliferation depending on the stress time. 16 These studies have demonstrated that mechanical loading can increase the diameter of the healed tendons by stimulating tenocyte proliferation and collagen synthesis, and so increase tensile strength. However, the precise physiological levels of strain, frequency, and duration to affect such a response are not well understood.Tendinopathy is a degenerative condition of uncertain etiology, although it is generally considered to be the result of tendon overuse. 17 However, there is increasing evidence that microtearing of tendon caused by general overuse might in fact lead to local understimulation of tenocytes and trigger the degenerative cascade of the tendon. 13,18,19 Clinical findings of tendon degeneration and c...

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Bone metabolic disorders include osteolysis, osteoporosis, osteoarthritis and rheumatoid arthritis. Osteoblasts and osteoclasts are two major types of cells in bone constituting homeostasis. The imbalance between bone formation by osteoblasts and bone resorption by osteoclasts has been shown to have a direct contribution to the onset of these diseases. Recent evidence indicates that autophagy and mitophagy, the selective autophagy of mitochondria, may play a vital role in regulating the proliferation, differentiation and function of osteoblasts and osteoclasts. Several signaling pathways, including PINK1/Parkin, SIRT1, MAPK8/FOXO3, Beclin-1/BECN1, p62/SQSTM1, and mTOR pathways, have been implied in the regulation of autophagy and mitophagy in these cells. Here we review the current progress about the regulation of autophagy and mitophagy in osteoblasts and osteoclasts in these bone metabolic disorders, as well as the molecular signaling activated or deactivated during this process. Together, we hope to draw attention to the role of autophagy and mitophagy in bone metabolic disorders, and their potential as a new target for the treatment of bone metabolic diseases and the requirements of further mechanism studies.