scholarly journals Altered paracrine signaling from the injured knee joint impairs postnatal long bone growth

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alberto Roselló-Díez ◽  
Daniel Stephen ◽  
Alexandra L Joyner
Keyword(s):  
Knee Joint ◽  
Internal Control ◽  
Bone Growth ◽  
Long Bone ◽  
Paracrine Signaling ◽  
Growth Modulation ◽  
Genetic Mouse Model ◽  
Mesenchyme Cells ◽  
Injured Knee ◽  
The Right

Regulation of organ growth is a poorly understood process. In the long bones, the growth plates (GPs) drive elongation by generating a scaffold progressively replaced by bone. Although studies have focused on intrinsic GP regulation, classic and recent experiments suggest that local signals also modulate GP function. We devised a genetic mouse model to study extrinsic long bone growth modulation, in which injury is specifically induced in the left hindlimb, such that the right hindlimb serves as an internal control. Remarkably, when only mesenchyme cells surrounding postnatal GPs were killed, left bone growth was nevertheless reduced. GP signaling was impaired by altered paracrine signals from the knee joint, including activation of the injury response and, in neonates, dampened IGF1 production. Importantly, only the combined prevention of both responses rescued neonatal growth. Thus, we identified signals from the knee joint that modulate bone growth and could underlie establishment of body proportions.

scholarly journals Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth in developing mice

2017 ◽  
Author(s):  
Alberto Roselló-Díez ◽  
Linda Madisen ◽  
Sébastien Bastide ◽  
Hongkui Zeng ◽  
Alexandra L. Joyner
Keyword(s):  
Internal Control ◽  
Bone Growth ◽  
Systemic Effect ◽  
Long Bone ◽  
Body Proportions ◽  
Compensatory Mechanisms ◽  
Left Limb ◽  
Catch Up ◽  
The Right ◽  
Systemic Responses

AbstractCatch-up growth after insults to growing organs is paramount to achieving robust body proportions. In fly larvae, local injury is followed by local and systemic compensatory mechanisms that allow damaged tissues to regain proportions with other tissues. In vertebrates, local catch-up growth has been described after transient reduction of bone growth, but the underlying cellular responses are controversial. We developed an approach to study catch-up growth in foetal mice by inducing mosaic expression of the cell cycle suppressor p21 in the cartilage cells (chondrocytes) that drive long bone elongation. By specifically targeting the left hindlimb, the right limb served as an internal control. Strikingly, left-right limb symmetry was not altered, revealing deployment of compensatory mechanisms. Above a certain threshold of insult, an orchestrated response was triggered involving local enhancement of bone growth and systemic growth reduction that ensured body proportions were maintained. The local response entailed hyper-proliferation of spared left-limb chondrocytes that was associated with reduced chondrocyte density. The systemic effect involved impaired placental IGF signalling and function, revealing bone-placenta communication. Thus, vertebrates, much like invertebrates, can mount coordinated local and systemic responses to developmental insults to ensure normal body proportions are maintained.

scholarly journals Langenskiöld Procedure for Treatment of Partial Growth Arrest of Distal Ulna After Septic Osteomyelitis: A Case Report

Hand ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. NP63-NP67
Author(s):  
Takashi Yoshida ◽  
Yoshinobu Oka ◽  
Atsushi Nishida ◽  
Hiroaki Wada ◽  
Wook-Cheol Kim
Keyword(s):  
Bone Growth ◽  
Growth Arrest ◽  
Growth Potential ◽  
Long Bone ◽  
Distal Ulna ◽  
Growth Impairment ◽  
Joint Infections ◽  
Shortening Osteotomy ◽  
The Right ◽  
Ulnar Lengthening

Background: Although cases of impaired long bone growth due to bone and joint infections in childhood are sometimes reported, few cases of growth impairment of the ulna due to septic osteomyelitis have been described. We report herein a case of ulnar partial physeal arrest treated using the Langenskiöld procedure. Materials and Methods: A boy developed septic osteomyelitis of the right distal ulna at age 2 years 6 months. Osteomyelitis subsided after antibiotic treatment and external immobilization. As a result of impaired growth of the ulna along the long axis, shortening and trumpet-shaped deformity of the metaphysis gradually appeared. Computed tomography revealed a bony bridge, and premature epiphyseal closure due to osteomyelitis was diagnosed. The Langenskiöld procedure was performed at 4 years 4 months old. Results: As of 2 years 9 months later, no further ulnar shortening has occurred and morphological remodeling has been confirmed. Conclusions: The treatments employed for ulnar shortening include ulnar lengthening by callotasis as well as stapling of the distal radial epiphyseal line or radial shortening osteotomy. In this case, the Langenskiöld procedure proved effective because the patient was still young with growth potential and the area of the bony bridge after osteomyelitis-induced epiphyseal line damage was <30%.

Biomechanical investigation of two long bone growth modulation techniques by finite element simulations

2017 ◽  
Vol 36 (5) ◽  
pp. 1398-1405 ◽  
Author(s):  
Manuel Schneider ◽  
Jan Buschbaum ◽  
Alexander Joeris ◽  
Oliver Röhrle ◽  
Jonathan Dwyer ◽  
...  
Keyword(s):  
Finite Element ◽  
Bone Growth ◽  
Finite Element Simulations ◽  
Long Bone ◽  
Growth Modulation ◽  
Biomechanical Investigation ◽  
Modulation Techniques

scholarly journals The role of intra-articular neuronal CCR2 receptors in knee joint pain associated with experimental osteoarthritis in mice

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Shingo Ishihara ◽  
Alia M. Obeidat ◽  
David L. Wokosin ◽  
Dongjun Ren ◽  
Richard J. Miller ◽  
...  
Keyword(s):  
Knee Joint ◽  
Sensory Neuron ◽  
Sensory Neurons ◽  
Direct Stimulation ◽  
Sensory Afferents ◽  
Neuronal Marker ◽  
The Right ◽  
Experimental Osteoarthritis ◽  
In Vivo Calcium Imaging

Abstract Background C–C chemokine receptor 2 (CCR2) signaling plays a key role in pain associated with experimental murine osteoarthritis (OA) after destabilization of the medial meniscus (DMM). Here, we aimed to assess if CCR2 expressed by intra-articular sensory neurons contributes to knee hyperalgesia in the early stages of the model. Methods DMM surgery was performed in the right knee of 10-week-old male wild-type (WT), Ccr2 null, or Ccr2RFP C57BL/6 mice. Knee hyperalgesia was measured using a Pressure Application Measurement device. CCR2 receptor antagonist (CCR2RA) was injected systemically (i.p.) or intra-articularly (i.a.) at different times after DMM to test its ability to reverse knee hyperalgesia. In vivo Ca2+ imaging of the dorsal root ganglion (DRG) was performed to assess sensory neuron responses to CCL2 injected into the knee joint cavity. CCL2 protein in the knee was measured by ELISA. Ccr2RFP mice and immunohistochemical staining for the pan-neuronal marker, protein gene product 9.5 (PGP9.5), or the sensory neuron marker, calcitonin gene-related peptide (CGRP), were used to visualize the location of CCR2 on intra-articular afferents. Results WT, but not Ccr2 null, mice displayed knee hyperalgesia 2–16 weeks after DMM. CCR2RA administered i.p. alleviated established hyperalgesia in WT mice 4 and 8 weeks after surgery. Intra-articular injection of CCL2 excited sensory neurons in the L4-DRG, as determined by in vivo calcium imaging; responses to CCL2 increased in mice 20 weeks after DMM. CCL2, but not vehicle, injected i.a. rapidly caused transient knee hyperalgesia in naïve WT, but not Ccr2 null, mice. Intra-articular CCR2RA injection also alleviated established hyperalgesia in WT mice 4 and 7 weeks after surgery. CCL2 protein was elevated in the knees of both WT and Ccr2 null mice 4 weeks after surgery. Co-expression of CCR2 and PGP9.5 as well as CCR2 and CGRP was observed in the lateral synovium of naïve mice; co-expression was also observed in the medial compartment of knees 8 weeks after DMM. Conclusions The findings suggest that CCL2-CCR2 signaling locally in the joint contributes to knee hyperalgesia in experimental OA, and it is in part mediated through direct stimulation of CCR2 expressed by intra-articular sensory afferents.

Dual Role of Caveolin-1 in β-Catenin Signaling During Fracture Healing Induced by Low-Intensity Pulsed Ultrasound in Rabbits

2021 ◽  
Vol 11 (2) ◽  
pp. 229-239
Author(s):  
Yun Li ◽  
Guanghua Liu ◽  
Feng Xiao ◽  
Wenqin Gu ◽  
Zhengdong Gao ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Molecular Mechanisms ◽  
Dual Role ◽  
Fracture Repair ◽  
Long Bone ◽  
Pulsed Ultrasound ◽  
Mineral Density ◽  
X Ray ◽  
Caveolin 1 ◽  
The Right

We did this research to observe the effect of LIPUS on long bone fracture repair and caveolin-1, β-catenin signaling expression in the radius defects of rabbits, to explore its possible molecular mechanisms. 24 male New Zealand rabbits with bilateral radial bone defects were divided into 4 groups randomly, n = 6. The right side had daily LIPUS exposure for 20 minutes, while the left received sham treatment. After 7, 14, 21, 28 days, respectively, fracture healing was observed by X-ray imaging and Dual Energy X-ray Absorptiometry (DXA) scan, specimens were harvested for histology, immunohistochemistry, and gene expression analysis. We found that LIPUS brought forward endochondral ossification, increased the bone callus size without changes in Bone Mineral Density (BMD). The caveolin-1 expression increased first then decreased, while the β-catenin kept growing during the process. These demonstrated that caveolin-1 participated in fracture healing accelerated by LIPUS, which was speculated to play a dual role in β-catenin signaling expression.

Application of the Motion Capture System in the Biomechanical Analysis of the Injured Knee Joint

2019 ◽  
pp. 257-265
Author(s):  
Jakub Otworowski ◽  
Tomasz Walczak ◽  
Adam Gramala ◽  
Jakub K. Grabski ◽  
Maurizio Tripi ◽  
...  
Keyword(s):  
Knee Joint ◽  
Motion Capture ◽  
Biomechanical Analysis ◽  
Motion Capture System ◽  
Injured Knee

Longitudinal bone growth in vitro: effects of insulin-like growth factor I and growth hormone

1991 ◽  
Vol 124 (5) ◽  
pp. 602-607 ◽  
Author(s):  
Ben A. A. Scheven ◽  
Nicola J. Hamilton
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Growth ◽  
Long Bone ◽  
Long Bones ◽  
Insulin Like Growth Factor ◽  
Serum Free ◽  
Factor I ◽  
Igf I

Abstract. Longitudinal growth was studied using an in vitro model system of intact rat long bones. Metatarsal bones from 18- and 19-day-old rat fetuses, entirely (18 days) or mainly (19 days) composed of chondrocytes, showed a steady rate of growth and radiolabelled thymidine incorporation for at least 7 days in serum-free media. Addition of recombinant human insulin-like growth factor-I to the culture media resulted in a direct stimulation of the longitudinal growth. Recombinant human growth hormone was also able to stimulate bone growth, although this was generally accomplished after a time lag of more than 2 days. A monoclonal antibody to IGF-I abolished both the IGF-I and GH-stimulated growth. However, the antibody had no effect on the growth of the bone explants in control, serum-free medium. Unlike the fetal long bones, bones from 2-day-old neonatal rats were arrested in their growth after 1-2 days in vitro. The neonatal bones responded to IGF-I and GH in a similar fashion as the fetal bones. Thus in this study in vitro evidence of a direct effect of GH on long bone growth via stimulating local production of IGF by the growth plate chondrocytes is presented. Furthermore, endogenous growth factors, others than IGFs, appear to play a crucial role in the regulation of fetal long bone growth.

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