• In endochondral bone formation, parathyroid hormone-related protein (PTHrP)-expressing RZSCs are the source of growth plate chondrocytes, which give rise to bone-forming osteoblasts as well as bone marrow skeletal stem cells 1 . (nature.com)
  • We show that perichondrial cells, which express abundant type I procollagen, and growth plate chondrocytes, which were found to express low amounts of type I procollagen, had ER stress and dysregulation of the same unfolded protein response pathway as previously demonstrated in osteoblasts. (jci.org)
  • Here we show that bone marrow endosteal SSCs are defined by fibroblast growth factor receptor 3 ( Fgfr3 ) and osteoblast-chondrocyte transitional (OCT) identities with some characteristics of bone osteoblasts and chondrocytes. (nature.com)
  • Of note, we define OCT identities as a state with some characteristics of both osteoblasts and chondrocytes, instead of cell-type plasticity between osteoblasts and chondrocytes. (nature.com)
  • This, in turn, precipitates chondrocyte apoptosis, thereby, osteoblasts invade the hypertrophic zone and bone formation occurs [ 5 ]. (pfmjournal.org)
  • Recently, a number of studies have confirmed that ADSCs possess the ability to differentiate into adipocytes, osteoblasts, and chondrocytes [ 16 - 18 ], suggesting that a broader source of stem cells is available for application in tissue engineering. (hindawi.com)
  • In the next years my lab will focus on determining the molecular mechanisms by which FGF signaling pathways control autophagy in chondrocytes and osteoblasts and on the identification of the physiological roles of autophagy in bone and cartilage. (ectsoc.org)
  • TGF-Beta is used to promote differentiation into chondrocytes and osteoblasts(although sometimes Bone Morphogenic Proteins can be used) so it is absolutely needed. (heightquest.com)
  • In this system however, osteoblast differentiation of PSCs is selectively inhibited by Sp7 deficiency but PSCs are still present and may still play a role in skeletal growth. (nature.com)
  • Aga2+/- proliferating chondrocytes showed increased FGF and MAPK signaling, findings consistent with accelerated differentiation. (jci.org)
  • There was also increased Sox9 expression throughout the growth plate, which is expected to accelerate early chondrocyte differentiation but reduce late hypertrophic differentiation. (jci.org)
  • The Hedgehog (Hh) signaling pathway regulates chondrocyte growth and differentiation in the growth plate. (umontreal.ca)
  • Indian hedgehog (IHH), one of its members, stimulates chondrocyte proliferation and osteoblast differentiation. (umontreal.ca)
  • This inhibits chondrocyte differentiation, and growth plate function is severely compromised. (medscape.com)
  • Growth, metabolism, and differentiation of chondrocytes, which are the key cellular players in this process, are regulated by systemic hormones, local factors, and cellular signaling pathways. (pfmjournal.org)
  • Local factors, including transcription factors such as SRY-box 9 protein (SOX9), Runt-related transcription factor 2 (RUNX2), and bone morphogenetic proteins (BMPs), along with signaling pathways such as the Wnt pathway, play critical roles in chondrocyte proliferation and differentiation. (pfmjournal.org)
  • Chondrocyte growth, metabolism, and differentiation are complex processes. (pfmjournal.org)
  • Site-1 protease is essential to growth plate maintenance and is a critical regulator of chondrocyte hypertrophic differentiation in postnatal mice. (nih.gov)
  • When cartilage is damaged, MSCs derived from synovial fluid can partially move to the injured site and differentiate into chondrocytes to repair the defect, and IGF-1 induces chondrogenic differentiation [ 11 , 12 , 13 ]. (biomedcentral.com)
  • IGF-1 is a member of a family of growth factors that are structurally closely related to pro-insulin and can promote chondrocyte proliferation, enhance matrix production, and inhibit chondrocyte apoptosis. (biomedcentral.com)
  • The disorder is caused by a dominantly inherited FGFR3 mutation that permanently activates the fibroblast growth factor receptor 3 (FGFR3) and its downstream mitogen-activated protein kinase (MAPK) signaling pathway. (medscape.com)
  • In particular, keeping in mind that the lysosomal-autophagy pathway is dynamically regulated in response to changes in the extracellular environment, my laboratory is exploring the hypothesis that the developmental regulation of this pathway is an important contributor to organismal development and growth. (ectsoc.org)
  • Currently, my laboratory is investigating the role of the lysosomal autophagy pathway during skeletal development and growth. (ectsoc.org)
  • The insulin-like growth factor (IGF) signaling pathway has been implicated in articular cartilage repair. (biomedcentral.com)
  • Here, we assessed whether VEGF is a critical downstream component of the HIF-1α-dependent survival pathway in chondrocytes. (ox.ac.uk)
  • Conclusion: These data show that chronic administration of MTX induces suppression of skeletal growth in mice, possibly through the inhibition of the pathway of de novo DNA synthesis. (elsevierpure.com)
  • Hypertrophic chondrocytes, a progeny of terminally differentiated chondrocytes from the proliferative zone, cease further proliferation, undergo hypertrophy in columns parallel to the axis of longitudinal elongation, and initiate the production of factors that trigger mineralization and vessel invasion. (pfmjournal.org)
  • Growth hormone (GH), sex hormone, thyroid hormone, as well as glucocorticoids affect chondrocyte proliferation and hypertrophy. (pfmjournal.org)
  • While hypertrophy of chondrocytes is a physiological process implicated in the longitudinal growth of long bones, hypertrophy-like alterations in chondrocytes play a major role in OA. (biomedcentral.com)
  • Chondrocyte hypertrophy is an essential process required for endochondral bone formation. (silverchair.com)
  • Proper regulation of chondrocyte hypertrophy is also required in postnatal cartilage homeostasis. (silverchair.com)
  • Indian hedgehog (Ihh) and PTHrP signaling play crucial roles in regulating the onset of chondrocyte hypertrophy by forming a negative feedback loop, in which Ihh signaling regulates chondrocyte hypertrophy by controlling PTHrP expression. (silverchair.com)
  • To understand whether there is a PTHrP -independent role of Ihh signaling in regulating chondrocyte hypertrophy, we have both activated and inactivated Ihh signaling in the absence of PTHrP during endochondral skeletal development. (silverchair.com)
  • We found that upregulating Ihh signaling in the developing cartilage by treating PTHrP -/- limb explants with sonic hedgehog (Shh) protein in vitro, or overexpressing Ihh in the cartilage of PTHrP -/- embryos or inactivating patched 1( Ptch1 ), a negative regulator of hedgehog (Hh) signaling, accelerated chondrocyte hypertrophy in the PTHrP -/- embryos. (silverchair.com)
  • Conversely, when Hh signaling was blocked by cyclopamine or by removing Smoothened ( Smo ), a positive regulator of Hh signaling,chondrocyte hypertrophy was delayed in the PTHrP -/- embryo. (silverchair.com)
  • Furthermore, we show that upregulated Hh signaling in the postnatal cartilage led to accelerated chondrocyte hypertrophy during secondary ossification, which in turn caused reduction of joint cartilage. (silverchair.com)
  • Our results revealed a novel role of Ihh signaling in promoting chondrocyte hypertrophy independently of PTHrP , which is particularly important in postnatal cartilage development and homeostasis. (silverchair.com)
  • In addition, we found that bone morphogenetic protein (Bmp) and Wnt/β-catenin signaling in the cartilage may both mediate the effect of upregulated Ihh signaling in promoting chondrocyte hypertrophy. (silverchair.com)
  • Using a combination of mouse genetics, cell biology and pharmacological approaches my lab has recently demonstrated that autophagy is induced in growth-plate chondrocytes during post-natal development and regulates the secretion of type II collagen (Col2), the major component of cartilage ECM. (ectsoc.org)
  • FGF signalling regulates bone growth through autophagy. (ectsoc.org)
  • Insulin-like growth factor-1 (IGF-1), a member of a family of growth factors that are structurally closely related to pro-insulin, has shown profound effects on chondrocyte biological behavior and fundamentally regulates cartilage matrix metabolism during cartilage repair. (biomedcentral.com)
  • The cartilaginous zone between primary and secondary ossification centers consists of well-arranged chondrocytes forming the physeal plate, allowing for postnatal growth in length of the long bones. (vin.com)
  • we applied Single-cell RNA sequencing (scRNA-seq) to delineate the comprehensive postnatal RC enthesis growth and the temporal atlas from as early as postnatal day 1 up to postnatal week 8. (elifesciences.org)
  • And, we furtherly performed single-cell spatial transcriptomic sequencing on postnatal day 1 mouse enthesis, in order to deconvolute bone-tendon junction (BTJ) chondrocytes onto spatial spots. (elifesciences.org)
  • The authors provided convincing evidence for the heterogeneity of postnatal enthesis growth and the molecular dynamics and signaling networks during enthesis formation. (elifesciences.org)
  • Link to all annotated objects annotated to positive regulation of growth plate cartilage chondrocyte proliferation. (planteome.org)
  • The regulation of chondrocyte function is mediated by several systemic, local, and cellular signaling pathways. (pfmjournal.org)
  • We decided to focus on the bone because the role that catabolic processes play in the regulation of skeletal growth has not been defined yet. (ectsoc.org)
  • During the 1950s and 1970s, many new bone dysplasias were identified based on clinical manifestations, radiographic findings, inheritance patterns, and morphology of the growth plate. (medscape.com)
  • The growth plate can be stratified into three distinct zones based on the size, morphology, orientation, proliferative potential, and function of chondrocytes: resting, proliferative, and hypertrophic zone. (pfmjournal.org)
  • Growth plate (physeal) fractures may be defined as disruptions in the cartilaginous physis of long bones that may or may not involve epiphyseal or metaphyseal bone. (medscape.com)
  • This chapter aims to elucidate that isotretinoin, given at various doses and durations, has been associated with growth plate abnormalities, which can lead to premature epiphyseal closure. (degruyter.com)
  • We included in our query reports of patients worldwide under 18 years of age with premature epiphyseal closure or growth plate damage secondary to isotretinoin. (degruyter.com)
  • Additionally, premature epiphyseal closure and growth plate abnormalities occurred in nine patients with various durations and doses of isotretinoin ranging from the lowest dose of 0.5 mg/kg/day for a few months to 3.5 mg/kg/day for years. (degruyter.com)
  • Isotretinoin-induced premature epiphyseal closure and growth plate deformities seem to be linked to higher doses of isotretinoin for the duration of months to years. (degruyter.com)
  • Disturbances in skeletal development can occur in each sequential step of skeletal development including cartilage growth, cartilage maturation and eventually mineralization, osteoid quality or osteoclast activity causing skeletal diseases as chondrodysplasia, osteochondrosis of growth plates and epiphyseal surface, osteogenesis imperfecta, and osteopetrosis. (vin.com)
  • Growth-plate fractures may lead to growth disorders due to destruction of epiphyseal circulation (inhibits physeal growth), or by the formation of a bone bridge across growth plate. (acrosspg.com)
  • A type V injury (illustrated below) is a compression or crush injury of the epiphyseal plate, with no associated epiphyseal or metaphyseal fracture. (acrosspg.com)
  • Thus, crosstalk between periosteal and growth plate stem cells is essential for post-developmental skeletal growth. (nature.com)
  • During skeletal growth, the heights of the plates, especially that of the hypertrophic zone, reflected the rate of bone growth. (ox.ac.uk)
  • Some hereditary diseases of extra-skeletal organs may have severe effects on skeletal growth or integrity. (vin.com)
  • The observation that mutations in more than 20 genes encoding for lysosomal proteins causes defects in skeletal growth in human suggests that lysosomal pathways play an important, yet unexplored, role during skeletogenesis. (ectsoc.org)
  • Aim: To investigate whether chronic administration of medium doses of methotrexate (MTX) causes suppression of skeletal growth in young mice and to determine whether folinic acid supplementation could reverse this effect. (elsevierpure.com)
  • Based on these observations, children suffering from juvenile rheumatoid arthritis, osteosarcoma or acute lymphoblastic leukaemia and receiving MTX over long periods of time could be at risk of short-term suppression of skeletal growth. (elsevierpure.com)
  • Achondroplasia is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene that leads to inhibited mineralization of chondrocytes (cartilage cells) in the growth plate. (medscape.com)
  • Vosoritide, a biologic analogue of C-type natriuretic peptide, prevents the inhibition of mineralization of chondrocytes caused by the FGFR3 mutation. (medscape.com)
  • In this study, we report a novel population of SSCs with osteoblast-chondrocyte transitional (OCT) identities in the bone marrow endosteal space, which highly expresses Fgfr3 and contributes to both normal and aberrant osteogenesis. (nature.com)
  • Achondroplasia is caused by mutations in the fibroblast growth factor receptor-3 ( FGFR3 ) gene. (medscape.com)
  • In this review, we summarized key regulatory factors and signaling pathways involved in chondrocyte functions, to understand how they affect chondrocyte growth and development. (pfmjournal.org)
  • We performed a quantitative proteomic analysis in osteoarthritic and normal chondrocytes followed by functional analyses to investigate proteome changes and molecular pathways involved in OA pathogenesis. (biomedcentral.com)
  • BMP-2 induces chondrocyte proliferation, endochondral bone formation, longitudinal bone growth, and bone and cartilage repair (6, 7). (novusbio.com)
  • When there is doubt, the injury should usually be considered a physeal or growth plate injury because of the potential for serious long-term complications (including growth arrest or deformity) with an occult physeal injury. (medscape.com)
  • Type III physeal injuries involve separations of portion of epiphysis and its associated growth plate from the rest of the epiphysis. (acrosspg.com)
  • These effects on endochondral ossification indicate that OI is a biologically complex phenotype going beyond its known impacts on bone to negatively affect linear growth. (jci.org)
  • The growth plate, a complex of cartilaginous structures situated between the epiphysis and the metaphysis of the long bones, orchestrates the process of endochondral ossification, which determines the linear growth of long bones [ 1 - 3 ]. (pfmjournal.org)
  • Proteoglycan desulfation determines the efficiency of chondrocyte autophagy and the extent of FGF signaling during endochondral ossification. (ectsoc.org)
  • Chondrocytes were isolated from articular cartilage of ten patients with primary OA undergoing knee replacement surgery and six normal donors undergoing fracture repair surgery without history of joint disease and no OA clinical manifestations. (biomedcentral.com)
  • Pathological changes initially occur in the articular cartilage, and later invade the subchondral bone plate and synovial tissues surrounding the joint. (spandidos-publications.com)
  • There are two types of growth plates: the epiphyses, which are at the ends of bones and provide longitudinal growth, and the apophyses, which are at the points of muscle attachments. (medscape.com)
  • Despite the continued presence of growth plates in aged rats, longitudinal growth no longer occurs. (ox.ac.uk)
  • Another study has demonstrated that both serum and synovial fluid from rheumatoid arthritis (RA) could not stimulate chondrocyte proteoglycan synthesis once the IGF-1 function was blocked by a primary antibody [ 6 ]. (biomedcentral.com)
  • We previously found that mice lacking the hypoxia-inducible transcription factor HIF-1α in cartilage show massive death of centrally located, hypoxic chondrocytes. (ox.ac.uk)
  • A similar phenotype was observed in mice with genetic ablation of either all or specifically the diffusible isoforms of vascular endothelial growth factor (VEGF), a prime angiogenic target of HIF-1α. (ox.ac.uk)
  • The effectiveness of the strategy was validated by showing that transgenic expression of VEGF164 in Col2-Cre;VEGF(f/f) mice stimulated angiogenesis in the perichondrium, fully corrected the excessive hypoxia of VEGF-deficient chondrocytes, and completely prevented chondrocyte death. (ox.ac.uk)
  • Yet, similarly crossed double-mutant embryos lacking HIF-1α and overexpressing VEGF164 in the growth plate cartilage still displayed a central cell death phenotype, albeit slightly delayed and less severe compared with mice exclusively lacking HIF-1α. (ox.ac.uk)
  • Such development pattern shares an overlapping biological behavior with the growth plate, which is a process of mesenchymal stem cells differentiating into chondrogenic cells and then sequentially into fibrocartilage cells ( Killian, 2022 ). (elifesciences.org)
  • This study provides evidence for further testing on the molecular mechanism of the disease and also propose proteins as candidate markers of OA chondrocyte phenotype. (biomedcentral.com)
  • Mammalian bone is formed through two distinct growth processes: endochondral and intramembranous bone formation 6 . (nature.com)
  • We narrowed our search to exclude patients with a history of growth plate disorders due to trauma, malignancy, or other pathological processes, as well as patients with growth arrest due to endocrine factors. (degruyter.com)
  • These studies will have the potential to identify new pathways through which growth factors regulate cellular catabolism, to explain how catabolic processes support anabolic pathways in vivo, and to provide proof of principle that developmental disorders may be treated by modulation of cellular metabolism. (ectsoc.org)
  • Thus, chondrocyte metabolism in the adjacent cartilage is relatively low, and these cells cannot easily migrate to the damaged site [ 2 ]. (biomedcentral.com)
  • Other approaches aiming for the regeneration of cartilage, make use of growth factors or cytokines, either by direct injection to the infected areas or using platelet-rich plasma or gene therapy approaches [ 10 , 13 - 15 ]. (biomedcentral.com)
  • Understanding molecular mechanisms underlying normal growth plate function has provided valuable insights into the genetic defects that impact growth and foundation for the development of effective therapeutic strategies for individuals with growth disorders. (pfmjournal.org)
  • These diseases include deficiency in growth hormone synthesis (dwarfism as in German Shepherd dogs), thyroid deficiency (as described in a family of Giant Schnauzers), and canine leucocyte adhesion deficiency (CLAD as in Irish Setters). (vin.com)
  • The resting zone, a source of stemlike progenitor cells that restores the reservoir of proliferative chondrocytes, is located farthest from the primary ossification center and assumes responsibility for preserving the architectural integrity of the growth plate [ 4 ]. (pfmjournal.org)
  • [ 2 ] These ligamentous structures are two to five times stronger than the growth plates at either end of a long bone and therefore are less often injured in children sustaining excessive external loads to the joints. (medscape.com)
  • Long bone growth is a fundamental determinant of final height. (pfmjournal.org)
  • Long bone growth plays a pivotal role in determining overall height. (pfmjournal.org)
  • Growth plate fractures account for 15-20% of major long-bone fractures and 34% of hand fractures in childhood. (acrosspg.com)
  • Salter-Harris is a commonly used method of describing fractures through the physis (growth plate) of skeletally immature individuals. (acrosspg.com)
  • Additionally, Indian hedgehog (Ihh) and C-type natriuretic peptide (CNP) are involved in the complex signaling network governing chondrocyte function. (pfmjournal.org)
  • Another important novel finding was made in 2000, when bone-derived hormone Fibroblast Growth Factor-23 (FGF23) was found to cause autosomal dominant hypophosphataemic rickets (ADHR), which provided the underlying mechanism for the previously unknown "phosphaturic factor" causing hypophosphataemia ( 2 , 3 ). (frontiersin.org)
  • Changes in any of these hormone axes can alter linear growth ( Fig. 1 ). (pfmjournal.org)
  • Protease breaks down peptide bonds that link amino acids together which means that it can break down compounds like Human Growth Hormone(growth hormone is peptide based)! (heightquest.com)
  • Periosteal stem cells (PSCs) and growth plate resting zone stem cells (RZSCs) critically contribute to intramembranous and endochondral bone formation, respectively. (nature.com)
  • Alternative therapies, including autologous chondrocyte implantation (ACI), matrix-induced ACI (MACI), and stem cell transplantation, are also available commercially or are in the clinical study phase. (biomedcentral.com)
  • Achondroplasia is a lifelong genetic condition resulting from the disordered skeletal architecture caused by impaired endochondral bone growth throughout childhood," added Polgreen, of the Lundquist Institute at Harbor and associate professor at the David Geffen School of Medicine, University of California, Los Angelas. (medscape.com)
  • As a parent of a child with achondroplasia, I see the availability of treatments that impact bone growth as an important step forward," said Amer Haider, co-founder of Growing Stronger, an organization with a mission to improve the quality of medical care for little people through supporting research, in the company press release. (medscape.com)
  • Standard growth curves for achondroplasia. (medscape.com)
  • Adapted from Horton WA, Rotter JI, Rimoin DL, et al: Standard growth curves for achondroplasia. (medscape.com)
  • Mean growth velocities (solid line) for males (top) and females (bottom) with achondroplasia compared to normal growth velocity curves. (medscape.com)
  • The large majority of these fractures heal without any impairment of growth mechanism but some lead to clinically important shortening and angulation. (acrosspg.com)
  • Mechanism: shear or fracture lines follow growth plate, separating epiphysis from metaphysis. (acrosspg.com)
  • Objective: Mechanotransduction is the mechanism that due to reacting chondrocytes on biomechanical loading of body mass. (ijbs.com)
  • Mechanotransduction is the mechanism which causes chondrocytes to react to the biomechanical loading of body mass [ 1 ]. (ijbs.com)
  • The protein content of BIO-MPM-1 is therefore less than 30 mg/L, and the medium contains no growth factors or hormones other than insulin. (bioind.com)