J Biosci Bioeng. 2017 Apr;123(4):512-522. Epub 2016 Nov 28. doi: 10.1016/j.jbiosc.2016.11.002.
Cell compaction influences the regenerative potential of passaged bovine articular chondrocytes in an ex vivo cartilage defect model
Michael Schmutzer, Attila Aszodi
Abstract: The loss and degradation of articular cartilage tissue matrix play central roles in the process of osteoarthritis (OA). New models for evaluating cartilage repair/regeneration are thus of great value for transferring various culture systems into clinically relevant situations. The repair process can be better monitored in ex vivo systems than in in vitro cell cultures. I have therefore established an ex vivo defect model prepared from bovine femoral condyles for evaluating cartilage repair by the implantation of cells cultured in various ways, e.g., monolayer-cultured cells or suspension or pellet cultures of articular bovine chondrocytes representing different cell compactions with variable densities of chondrocytes. I report that the integrin subunit α10 was significantly upregulated in suspension-cultured bovine chondrocytes at passage P2 compared with monolayer-cultured cells at P1 (p = 0.0083) and P2 (p < 0.05). Suspension-cultured cells did not promote cartilage repair when compared with implanted monolayer-cultured chondrocytes and pellets: 24.0 ± 0.66% for suspension cells, 46.4 ± 2.9% for monolayer cells, and 127.64 ± 0.90% for pellets (p < 0.0001) of the original defect volume (percentage of defect). Additional cultivation with chondrogenesis-promoting growth factors TGF-β1 and BMP-2 revealed an enhancing effect on cartilage repair in all settings. The advantage and innovation of this system over in vitro differentiation (e.g., micromass, pellet) assays is the possibility of examining and evaluating cartilage regeneration in an environment in which implanted cells are embedded within native surrounding tissue at the defect site. Such ex vivo explants might serve as a better model system to mimic clinical situations.
Int J Mol Sci. 2017 Apr 28;18(5):931. doi: 10.3390/ijms18050931.
Peripheral Nerve Fibers and Their Neurotransmitters in Osteoarthritis Pathology
Susanne Grässel, Dominique Muschter
Abstract: The importance of the nociceptive nervous system for maintaining tissue homeostasis has been known for some time, and it has also been suggested that organogenesis and tissue repair are under neuronal control. Changes in peripheral joint innervation are supposed to be partly responsible for degenerative alterations in joint tissues which contribute to development of osteoarthritis. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters, allowing response to peripheral neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells and chondrocytes of different origin, which express distinct subtypes of adrenoceptors (AR), receptors for vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). Some of these cell types synthesize and secrete neuropeptides such as SP, and they are positive for tyrosine-hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters are involved in the pathology of inflammatory diseases such as rheumatoid arthritis (RA) which manifests mainly in the joints. In addition, they seem to play a role in pathogenesis of priori degenerative joint disorders such as osteoarthritis (OA). Altogether it is evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for joint tissue and bone homeostasis. They modulate articular cartilage, subchondral bone and synovial tissue properties in physiological and pathophysiological conditions, in addition to their classical neurological features.
Cartilage Vol. 2 Chapter 10 Page 191-227 Springer February 2017. doi: 10.1007/978-3-319-45803-8_9.
The Sensory and Sympathetic Nervous System in Cartilage Physiology and Pathophysiology
Grässel Susanne, Straub Rainer, Jenei-Lanzl Zsuzsa
Abstract: The peripheral nervous system is critically involved in metabolism of joint tissue and intervertebral disks (IVD). Nerve fibers of sympathetic and sensory origin innervate synovial tissue and subchondral bone of diarthrodial joints. In pathophysiological situations as in osteoarthritis (OA), rheumatoid arthritis (RA), and IVD degeneration, innervation patterns of sympathetic and sensory nerve fibers are partly altered in joint tissue and IVD. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters allowing response to neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells, and different types of chondrocytes, which express distinct subtypes of adrenoceptors, receptors for vasoactive intestinal peptide (VIP), for substance P (SP), and calcitonin gene-related peptide (CGRP). Some of these cell types even synthesize neuropeptides such as SP, and they are positive for tyrosine hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. During endochondral ossification in embryonic limb development, sensory and sympathetic neurotransmitters modulate osteo-chondrogenic differentiation of mesenchymal progenitor cells, vascularization, and matrix differentiation indicating a distinct role in skeletal growth and possible limb regeneration processes. In adults, sensory and sympathetic neurotransmitters are involved in pathology of inflammatory diseases as rheumatoid arthritis which manifests mainly in joints. In addition, they might play a role in pathogenesis of a priori degenerative joint disorders, as osteoarthritis and intervertebral disk degeneration. Altogether it became evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for proper limb formation during embryonic skeletal growth. In adults, they modulate articular cartilage, subchondral bone and synovial tissue homeostasis, and physiological and pathophysiological conditions, in addition to their classical neurological features.