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Developmental Dynamics : An Official... Jun 2022The axolotl is a key model to study appendicular regeneration. The limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs...
BACKGROUND
The axolotl is a key model to study appendicular regeneration. The limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs develop postembryonically. In this work, we evaluated the postembryonic development of the appendicular skeleton and its changes with aging.
RESULTS
The juvenile limb skeleton is formed mostly by Sox9/Col1a2 cartilage cells. Ossification of the appendicular skeleton starts when animals reach a length of 10 cm, and cartilage cells are replaced by a primary ossification center, consisting of cortical bone and an adipocyte-filled marrow cavity. Vascularization is associated with the ossification center and the marrow cavity formation. We identified the contribution of Col1a2-descendants to bone and adipocytes. Moreover, ossification progresses with age toward the epiphyses of long bones. Axolotls are neotenic salamanders, and still ossification remains responsive to l-thyroxine, increasing the rate of bone formation.
CONCLUSIONS
In axolotls, bone maturation is a continuous process that extends throughout their life. Ossification of the appendicular bones is slow and continues until the complete element is ossified. The cellular components of the appendicular skeleton change accordingly during ossification, creating a heterogenous landscape in each element. The continuous maturation of the bone is accompanied by a continuous body growth.
Topics: Aging; Ambystoma mexicanum; Animals; Bone Development; Bone and Bones; Osteogenesis
PubMed: 34322944
DOI: 10.1002/dvdy.407 -
Current Topics in Developmental Biology 2019The joints are a diverse group of skeletal structures, and their genesis, morphogenesis, and acquisition of specialized tissues have intrigued biologists for decades.... (Review)
Review
The joints are a diverse group of skeletal structures, and their genesis, morphogenesis, and acquisition of specialized tissues have intrigued biologists for decades. Here we review past and recent studies on important aspects of joint development, including the roles of the interzone and morphogenesis of articular cartilage. Studies have documented the requirement of interzone cells in limb joint initiation and formation of most, if not all, joint tissues. We highlight these studies and also report more detailed interzone dissection experiments in chick embryos. Articular cartilage has always received special attention owing to its complex architecture and phenotype and its importance in long-term joint function. We pay particular attention to mechanisms by which neonatal articular cartilage grows and thickens over time and eventually acquires its multi-zone structure and becomes mechanically fit in adults. These and other studies are placed in the context of evolutionary biology, specifically regarding the dramatic changes in limb joint organization during transition from aquatic to land life. We describe previous studies, and include new data, on the knee joints of aquatic axolotls that unlike those in higher vertebrates, are not cavitated, are filled with rigid fibrous tissues and resemble amphiarthroses. We show that when axolotls metamorph to life on land, their intra-knee fibrous tissue becomes sparse and seemingly more flexible and the articular cartilage becomes distinct and acquires a tidemark. In sum, there have been considerable advances toward a better understanding of limb joint development, biological responsiveness, and evolutionary influences, though much remains unclear. Future progress in these fields should also lead to creation of new developmental biology-based tools to repair and regenerate joint tissues in acute and chronic conditions.
Topics: Animals; Biological Evolution; Bone and Bones; Cartilage, Articular; Cell Lineage; Humans; Joints; Morphogenesis
PubMed: 30902250
DOI: 10.1016/bs.ctdb.2018.11.002 -
Journal of Cellular Physiology May 2022Currently, there is no consensus whether there is a single or multiple postnatal stem cell population(s) that contribute to skeletal homeostasis and postnatal bone...
Currently, there is no consensus whether there is a single or multiple postnatal stem cell population(s) that contribute to skeletal homeostasis and postnatal bone formation. A known population of cells that express Prx1 contributes to postnatal bone formation. Prx1 expression also connotes calvaria and appendicular tissues during embryonic development. A transgenic tamoxifen inducible Prx1 reporter mouse was used for lineage tracking, to characterize the postnatal contribution of Prx1 expressing cells in skeletal homeostasis and bone formation. Under homeostatic conditions Prx1 labeling gave rise to a transient yet rapid turnover cell population at the periosteal and endosteal surfaces, along muscle fibers, and within the medial layers of vessels both within the muscle and marrow compartments of the appendicular skeleton. Fracture and ectopic bone formation of both fore and hind limbs showed recruitment and expansion of Prx1-derived cells in newly formed bone tissues. Prx1 labeled cells were limited or absent at axial skeletal sites during both homeostasis and after induction of bone formation. Last, Prx1-derived cells differentiated into multiple cell lineages including vascular smooth muscle, adipose, cartilage, and bone cells. These results show that Prx1 expression retained its embryonic tissue specification and connotes a stem/progenitor cell populations of mesenchymal tissue progenitors.
Topics: Animals; Cartilage; Cell Differentiation; Cell Lineage; Female; Homeodomain Proteins; Mice; Mice, Transgenic; Pregnancy; Skull; Stem Cells
PubMed: 35338481
DOI: 10.1002/jcp.30728 -
Acta Orthopaedica Et Traumatologica... Nov 2022The purpose of this study was to investigate the results and complications in patients who had low-grade chondrosarcomas in the appendicular skeleton and were treated by...
OBJECTIVE
The purpose of this study was to investigate the results and complications in patients who had low-grade chondrosarcomas in the appendicular skeleton and were treated by intralesional curettage and cementation within the scope of 25 years of experience in a single center.
METHODS
Ninety-one patients (72 female and 19 male) were retrospectively analyzed. The median at the time of surgery was 43 (17-78) years, and the median follow-up was 102 (26-288) months. All patients were treated by intralesional curettage followed by cementation with high-viscosity bone cement (polymethylmethacrylate). Complications and local recurrence rates, as well as clinical outcome scores were recorded.
RESULTS
Five patients (5.49%) developed local recurrence at an average of 6.6 (6-9) months postoperatively. Four were treated with local wide excision and reconstruction with tumor prosthesis. One patient received recurettage and cementation. Two recurred patients were dedifferentiated into grade II chondrosarcomas in the last intervention. No major postoperative complication was identified in the series. Patients achieved an average Musculoskeletal Tumor Society scoring system of 92.4% (standard deviation 5.2; range 80-100) in the sixth postoperative month. Musculoskeletal Tumor Society scores in the recurrent patients decreased from an average of 90% to 75.3% after the final intervention.
CONCLUSION
Intralesional curettage and cementation seem safe and reliable techniques with low recurrence and complication rates in treating low-grade chondrosarcomas of the appendicular skeleton. Clinical, radiological, and pathological evaluations are mandatory before surgical intervention, and a multidisciplinary approach is crucial. A strict follow-up regimen in the early postoperative period is needed and strongly recommended to detect local recurrence.
LEVEL OF EVIDENCE
Level IV, Therapeutic Study.
Topics: Humans; Male; Female; Bone Neoplasms; Retrospective Studies; Cementation; Chondrosarcoma; Curettage; Neoplasm Recurrence, Local; Treatment Outcome
PubMed: 36567544
DOI: 10.5152/j.aott.2022.22091 -
Genesis (New York, N.Y. : 2000) Sep 2022Craniofacial and appendicular bone homeostasis is dynamically regulated by a balance between bone formation and resorption by osteoblasts and osteoclasts, respectively.... (Review)
Review
Craniofacial and appendicular bone homeostasis is dynamically regulated by a balance between bone formation and resorption by osteoblasts and osteoclasts, respectively. Despite the developments in multiple imaging techniques in bone biology, there are still technical challenges and limitations in the investigation of spatial/anatomical location of rare stem/progenitor cells and their molecular regulation in tooth and craniofacial bones of living animals. Recent advances in live animal imaging techniques for the craniofacial and dental apparatus can provide new insights in real time into bone stem/progenitor cell dynamics and function in vivo. Here, we review the current inventions and applications of the noninvasive intravital imaging technique and its practical uses and limitations in the analysis of stem/progenitor cells in craniofacial and dental apparatus in vivo. Furthermore, we also explore the potential applications of intravital microscopy in the dental field.
Topics: Animals; Bone and Bones; Intravital Microscopy; Molecular Imaging; Osteoclasts; Stem Cells
PubMed: 35980285
DOI: 10.1002/dvg.23498 -
Journal of Molecular Endocrinology Jul 2018The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily... (Review)
Review
The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily among endocrinologists who study growth and metabolism. The advancement of molecular endocrinology over the past four decades enables investigators to re-examine and refine the established somatomedin hypothesis. Specifically, gene deletions, transgene overexpression or more recently, cell-specific gene-ablations, have enabled investigators to study the effects of the and genes in temporal and spatial manners. The GH/IGF axis, acting in an endocrine and autocrine/paracrine fashion, is the major axis controlling skeletal growth. Studies in rodents have clearly shown that IGFs regulate bone length of the appendicular skeleton evidenced by changes in chondrocytes of the proliferative and hypertrophic zones of the growth plate. IGFs affect radial bone growth and regulate cortical and trabecular bone properties via their effects on osteoblast, osteocyte and osteoclast function. Interactions of the IGFs with sex steroid hormones and the parathyroid hormone demonstrate the significance and complexity of the IGF axis in the skeleton. Finally, IGFs have been implicated in skeletal aging. Decreases in serum IGFs during aging have been correlated with reductions in bone mineral density and increased fracture risk. This review highlights many of the most relevant studies in the IGF research landscape, focusing in particular on IGFs effects on the skeleton.
Topics: Animals; Chondrocytes; Humans; Osteoblasts; Osteoclasts; Skeleton; Somatomedins
PubMed: 29626053
DOI: 10.1530/JME-17-0298 -
Autophagy Jan 2014From an evolutionary perspective, the major function of bone is to provide stable sites for muscle attachment and affording protection of vital organs, especially the... (Review)
Review
From an evolutionary perspective, the major function of bone is to provide stable sites for muscle attachment and affording protection of vital organs, especially the heart and lungs (ribs) and spinal cord (vertebrae and intervertebral discs). However, bone has a considerable number of other functions: serving as a store for mineral ions, providing a site for blood cell synthesis and participating in a complex system-wide endocrine system. Not surprisingly, bone and cartilage cell homeostasis is tightly controlled, as is the maintenance of tissue structure and mass. While a great deal of new information is accruing concerning skeletal cell homeostasis, one relatively new observation is that the cells of bone (osteoclasts osteoblasts and osteocytes) and cartilage (chondrocytes) exhibit autophagy. The focus of this review is to examine the significance of this process in terms of the functional demands of the skeleton in health and during growth and to provide evidence that dysregulation of the autophagic response is involved in the pathogenesis of diseases of bone (Paget disease of bone) and cartilage (osteoarthritis and the mucopolysaccharidoses). Delineation of molecular changes in the autophagic process is uncovering new approaches for the treatment of diseases that affect the axial and appendicular skeleton.
Topics: Animals; Autophagy; Bone Diseases; Bone and Bones; Cartilage; Humans; Osteoclasts; Osteocytes
PubMed: 24225636
DOI: 10.4161/auto.26679 -
Journal of Bone and Mineral Research :... Dec 2023Patients with classical melorheostosis exhibit exuberant bone overgrowth in the appendicular skeleton, resulting in pain and deformity with no known treatment. Most...
Patients with classical melorheostosis exhibit exuberant bone overgrowth in the appendicular skeleton, resulting in pain and deformity with no known treatment. Most patients have somatic, mosaic mutations in MAP2K1 (encoding the MEK1 protein) in osteoblasts and overlying skin. As with most rare bone diseases, lack of affected tissue has limited the opportunity to understand how the mutation results in excess bone formation. The aim of this study was to create a cellular model to study melorheostosis. We obtained patient skin cells bearing the MAP2K1 mutation (affected cells), and along with isogenic control normal fibroblasts reprogrammed them using the Sendai virus method into induced pluripotent stem cells (iPSCs). Pluripotency was validated by marker staining and embryoid body formation. iPSCs were then differentiated to mesenchymal stem cells (iMSCs) and validated by flow cytometry. We confirmed retention of the MAP2K1 mutation in iMSCs with polymerase chain reaction (PCR) and confirmed elevated MEK1 activity by immunofluorescence staining. Mutation-bearing iMSCs showed significantly elevated vascular endothelial growth factor (VEGF) secretion, proliferation and collagen I and IV secretion. iMSCs were then differentiated into osteoblasts, which showed increased mineralization at 21 days and increased VEGF secretion at 14 and 21 days of differentiation. Administration of VEGF to unaffected iMSCs during osteogenic differentiation was sufficient to increase mineralization. Blockade of VEGF by bevacizumab reduced mineralization in iMSC-derived affected osteoblasts and in affected primary patient-derived osteoblasts. These data indicate that patient-derived induced pluripotent stem cells recreate the elevated MEK1 activity, increased mineralization, and increased proliferation seen in melorheostosis patients. The increased bone formation is driven, in part, by abundant VEGF secretion. Modifying the activity of VEGF (a known stimulator of osteoblastogenesis) represents a promising treatment pathway to explore. iPSCs may have wide applications to other rare bone diseases. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Bone and Bones; Cell Differentiation; MAP Kinase Kinase 1; Melorheostosis; Osteogenesis; Vascular Endothelial Growth Factor A
PubMed: 37737377
DOI: 10.1002/jbmr.4915