Re-examining osteoarthritis therapy from a developmental biologist's perspective.

Osteoarthritis is the most prevalent musculoskeletal disorder and one for which there is no disease modifying therapy available at present. Our current understanding of the disease mechanism of osteoarthritis is limited owing to a lacuna of knowledge about the development and maintenance of articular cartilage that is affected during osteoarthritis. All current therapeutic strategies aim at countering inflammation which though mitigates pain but does not arrest the progressive degeneration of articular cartilage. During osteoarthritis, articular cartilage expresses markers for transient cartilage differentiation. Moreover, blocking transient cartilage differentiation is sufficient for halting the progression of experimental osteoarthritis. A developmental biology inspired approach that combines restoration of tissue microenvironment, supplementation with engineered cartilage and built in mechanism to prevent transient cartilage differentiation could be an avenue for developing a disease modifying therapy for osteoarthritis.

• Publication year

  2019

• Venue

  Biochemical Pharmacology

• Publication date

  2019-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.bcp.2019.03.020PMID 30922620
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• BMP signaling‐driven osteogenesis is critically dependent on Prdx‐1 expression‐mediated maintenance of chondrocyte prehypetrophy

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• Cartilage degradation in osteoarthritis: A process of osteochondral remodeling resembles the endochondral ossification in growth plate?

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• Regeneration of plantlets through somatic embryogenesis from root derived calli of Hibiscus sabdariffa L. (Roselle) and assessment of genetic stability by flow cytometry and ISSR analysis

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• Precise spatial restriction of BMP signaling in developing joints is perturbed upon loss of embryo movement

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• Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis

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• Wnt signaling in cartilage development and diseases: lessons from animal studies

  2016cited by this paper
• Chondromodulin-1 ameliorates osteoarthritis progression by inhibiting HIF-2α activity.

  2016cited by this paper
• A top-notch dilemma: The complex role of NOTCH signaling in osteoarthritis

  2015cited by this paper
• Dual pathways to endochondral osteoblasts: a novel chondrocyte-derived osteoprogenitor cell identified in hypertrophic cartilage

  2015cited by this paper
• Strategies to minimize hypertrophy in cartilage engineering and regeneration

  2015cited by this paper
• A dual role for NOTCH signaling in joint cartilage maintenance and osteoarthritis

  2015cited by this paper
• Precise spatial restriction of BMP signaling is essential for articular cartilage differentiation

  2015cited by this paper
• A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation

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• Disrupting the Indian hedgehog signaling pathway in vivo attenuates surgically induced osteoarthritis progression in Col2a1-CreERT2; Ihhfl/fl mice

  2014cited by this paper
• Elevated VEGF levels contribute to the pathogenesis of osteoarthritis

  2014cited by this paper
• Type X collagen levels are elevated in serum from human osteoarthritis patients and associated with biomarkers of cartilage degradation and inflammation

  2014cited by this paper
• Identification of mechanosensitive genes during skeletal development: alteration of genes associated with cytoskeletal rearrangement and cell signalling pathways

  2014cited by this paper
• Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation

  2014cited by this paper
• Genesis and morphogenesis of limb synovial joints and articular cartilage.

  2014cited by this paper
• RBP-Jκ-dependent Notch signaling is required for murine articular cartilage and joint maintenance.

  2013cited by this paper
• Extended report: Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial

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• Inhibition of TGF–β signaling in subchondral bone mesenchymal stem cells attenuates osteoarthritis

  2013cited by this paper
• Interplay between Cartilage and Subchondral Bone Contributing to Pathogenesis of Osteoarthritis

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• New findings in osteoarthritis pathogenesis: therapeutic implications

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• The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments?

  2013cited by this paper
• Tissue engineering approaches for osteoarthritis.

  2012cited by this paper
• Expression patterns of Notch receptors and their ligands in human osteoarthritic and healthy articular cartilage.

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• Can one generate stable hyaline cartilage from adult mesenchymal stem cells? A developmental approach

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• Molecular differentiation between osteophytic and articular cartilage--clues for a transient and permanent chondrocyte phenotype.

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• Unlike Bone, Cartilage Regeneration Remains Elusive

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• Subchondral bone as a key target for osteoarthritis treatment.

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• Cartilage biology in osteoarthritis—lessons from developmental biology

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• Current Surgical Treatment of Knee Osteoarthritis

  2011cited by this paper
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  2011cited by this paper
• ADAMTS‐4 and ADAMTS‐5: Key enzymes in osteoarthritis

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• Tissue engineering of functional articular cartilage: the current status

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• The role of the Notch pathway in healthy and osteoarthritic articular cartilage: from experimental models to ex vivo studies

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• The role of the cartilage matrix in osteoarthritis

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• Expression of Vascular Endothelial Growth Factor (VEGF) Associated with Histopathological Changes in Rodent Models of Osteoarthritis

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• Hypertrophic differentiation of chondrocytes in osteoarthritis: the developmental aspect of degenerative joint disorders

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• Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis

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• Surgical management of osteoarthritis

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• Inhibition of osteoclasts prevents cartilage loss and pain in a rat model of degenerative joint disease.

  2010cited by this paper
• Non-pharmacological approaches for the treatment of osteoarthritis.

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• The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study.

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• Transient activation of Wnt/{beta}-catenin signaling induces abnormal growth plate closure and articular cartilage thickening in postnatal mice.

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• Activation of β‐Catenin Signaling in Articular Chondrocytes Leads to Osteoarthritis‐Like Phenotype in Adult β‐Catenin Conditional Activation Mice

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• Missense mutations in IHH impair Indian Hedgehog signaling in C3H10T1/2 cells: Implications for brachydactyly type A1, and new targets for Hedgehog signaling

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• Muscle contraction is necessary to maintain joint progenitor cell fate.

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• Modulating hedgehog signaling can attenuate the severity of osteoarthritis

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• The Basic Science of Articular Cartilage

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• Inhibition of β-catenin signaling causes defects in postnatal cartilage development

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• Inhibition of beta-catenin signaling in articular chondrocytes results in articular cartilage destruction.

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• Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound?

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• Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification

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• Expression of bone resorption genes in osteoarthritis and in osteoporosis

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• Osteophytes: relevance and biology.

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• Expression of collagen type I and type II in consecutive stages of human osteoarthritis

  2004cited by this paper
• Osteoarthritis--the impact of a serious disease.

  2004cited by this paper
• BMP Receptor Signaling Is Required for Postnatal Maintenance of Articular Cartilage

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• Response of joint structures to inactivity and to reloading after immobilization.

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• Developmental regulation of the growth plate

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• Expression of the cartilage derived anti-angiogenic factor chondromodulin-I decreases in the early stage of experimental osteoarthritis.

  2003cited by this paper
• Development and regulation of osteophyte formation during experimental osteoarthritis.

  2002cited by this paper
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  2001cited by this paper
• Wnt-14 plays a pivotal role in inducing synovial joint formation in the developing appendicular skeleton.

  2001cited by this paper
• Articular cartilage and changes in Arthritis: Cell biology of osteoarthritis

  2001cited by this paper
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  2000cited by this paper
• Dual roles of Wnt signaling during chondrogenesis in the chicken limb.

  2000cited by this paper
• Review: tissue engineering for regeneration of articular cartilage.

  2000cited by this paper
• VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation

  1999cited by this paper
• Sox9 is required for cartilage formation

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• Evidence for altered synthesis of type II collagen in patients with osteoarthritis.

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• Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton.

  1998cited by this paper
• Distinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage.

  1997cited by this paper
• Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage.

  1997cited by this paper
• Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein

  1996cited by this paper
• Isolation and characterization of two sialoproteins present only in bone calcified matrix.

  1985cited by this paper
• Hypothesis: joints can heal.

  1984cited by this paper

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