scholarly journals Chondrogenesis mediates progression of ankylosing spondylitis through heterotopic ossification

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Tao Yu ◽  
Jianguo Zhang ◽  
Wei Zhu ◽  
Xiao Wang ◽  
Yun Bai ◽  
...  

AbstractAnkylosing spondylitis (AS) is chronic inflammatory arthritis with a progressive fusion of axial joints. Anti-inflammatory treatments such as anti-TNF-α antibody therapy suppress inflammation but do not effectively halt the progression of spine fusion in AS patients. Here we report that the autoimmune inflammation of AS generates a microenvironment that promotes chondrogenesis in spine ligaments as the process of spine fusion. Chondrocyte differentiation was observed in the ligaments of patients with early-stage AS, and cartilage formation was followed by calcification. Moreover, a large number of giant osteoclasts were found in the inflammatory environment of ligaments and on bony surfaces of calcified cartilage. Resorption activity by these giant osteoclasts generated marrow with high levels of active TGF-β, which induced new bone formation in the ligaments. Notably, no Osterix+ osteoprogenitors were found in osteoclast resorption areas, indicating uncoupled bone resorption and formation. Even at the late and maturation stages, the uncoupled osteoclast resorption in bony interspinous ligament activates TGF-β to induce the progression of ossification in AS patients. Osteoclast resorption of calcified cartilage-initiated ossification in the progression of AS is a similar pathologic process of acquired heterotopic ossification (HO). Our finding of cartilage formation in the ligaments of AS patients revealed that the pathogenesis of spinal fusion is a process of HO and explained why anti-inflammatory treatments do not slow ankylosing once there is new bone formation in spinal soft tissues. Thus, inhibition of HO formation, such as osteoclast activity, cartilage formation, or TGF-β activity could be a potential therapy for AS.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1832.2-1833
Author(s):  
J. De Jongh ◽  
R. Hemke ◽  
G. C. J. Zwezerijnen ◽  
M. Yaqub ◽  
I. Van der Horst-Bruinsma ◽  
...  

Background:Bone formation in spondyloarthritis (SpA) is presumably related to local enthesitis/peri-articular inflammation and ultimately may lead to functional limitation (1,2). X-rays only allow long-term monitoring of bone formation (≥2 years) (3). Imaging techniques that can visualize bone formation at an early stage would therefore be valuable. Positron Emission Tomography (PET) using [18F]Fluoride can visualize and quantify (early changes in) bone formation at molecular level (4).Objectives:To investigate the feasibility of [18F]Fluoride to assess new bone formation at axial and peripheral enthesial sites in SpA patients.Methods:Thus far, 5 of the total of 15 patients with clinically active ankylosing spondylitis (AS) (according to modified New York criteria and BASDAI ≥4) and 8 of the 25 patients with active psoriatic arthritis (PsA) (according to CASPAR criteria and ≥1 clinically active enthesitis) were included. Of each patient, a whole body [18F]Fluoride PET-CT scan was performed. All scans were visually judged and scored dichotomously by one reader (blinded for clinical data) for PET-positive lesions in the spine, peripheral enthesis sites and joints. Low dose CT was used for anatomical reference.Results:The study is ongoing, with whole body [18F]Fluoride PET-CT scans available in five AS patients and eight PsA patients. In 4/5 AS scans, at least (≥1) PET positive lesions were found in the cervical, thoracic and/or lumbar vertebrae. These were mainly found in anterior corners of vertebrae and bridging syndesmophytes (Fig. 1A). In all eight PsA patients, at least 1 PET positive lesion was visualized, projected either at the site of a tendon attachment (fascia plantaris, achilles- and patella tendon (Fig 1B)) or peri-articularly (in the ankle or wrist).Fig 1.[18F]Fluoride uptake in the cervical, thoracic and lumbar spine in a clinically active AS patient (A) and in the patella tendon of the right knee in a clinically active PsA patient (B)Conclusion:[18F]Fluoride PET uptake, reflecting new bone formation, can be visualized at heterogeneously distributed enthesis and (peri-)articular sites in AS- and PsA patients. The technique therefore is sensitive to visualize new bone formation and may reflect local disease activity. Additional scans will be collected and analyzed quantitatively, also after anti-TNF or Secukinumab treatment, to further investigate the applicability of [18F]Fluoride PET for monitoring of therapeutic effects on bone formation in SpA.References: :[1]Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, et al. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009;68(6):948-53.[2]Rezvani A, Bodur H, Ataman S, Kaya T, Bugdayci DS, Demir SE, et al. Correlations among enthesitis, clinical, radiographic and quality of life parameters in patients with ankylosing spondylitis. Mod Rheumatol. 2014;24(4):651-6.[3]Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum 2005;52:1000-8..[4]Bruijnen ST, Verweij NJF, van Duivenvoorde L, Bravenboer N, Baeten D, van Denderen JC, et al. [18F]Fluoride PET-CT imaging of bone formation in ankylosing spondylitis before and after 12 weeks of anti-TNF treatment. 2017.Acknowledgments:We thank EULAR Foreum, Pfizer and Novartis for financial support of this investigator initiated study.Disclosure of Interests:Jerney de Jongh: None declared, Robert Hemke: None declared, Gerben C.J. Zwezerijnen: None declared, Maqsood Yaqub: None declared, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Marleen G.H. van de Sande Grant/research support from: Novartis, Eli lily, UCB, Jansen, Consultant of: Abbvie, Novartis, Eli lily, MSD, Arno Van Kuijk: None declared, Irene Bultink: None declared, Lot Burgemeister: None declared, Nancy M.A. van Dillen: None declared, Alexandre Voskuyl: None declared, Conny J. van der Laken: None declared


2008 ◽  
Vol 396-398 ◽  
pp. 7-10 ◽  
Author(s):  
Ana Maria Minarelli Gaspar ◽  
Sybele Saska ◽  
R. García Carrodeguas ◽  
A.H. De Aza ◽  
P. Pena ◽  
...  

The biological response following subcutaneous and bone implantation of β-wollastonite(β-W)-doped α-tricalcium phosphate bioceramics in rats was evaluated. Tested materials were: tricalcium phosphate (TCP), consisting of a mixture of α- and β-polymorphs; TCP doped with 5 wt. % of β-W (TCP5W), composed of α-TCP as only crystalline phase; and TCP doped with 15 wt. % of β-W (TCP15), containing crystalline α-TCP and β-W. Cylinders of 2x1 mm were implanted in tibiae and backs of adult male Rattus norvegicus, Holtzman rats. After 7, 30 and 120 days, animals were sacrificed and the tissue blocks containing the implants were excised, fixed and processed for histological examination. TCP, TCP5W and TCP15W implants were biocompatible but neither bioactive nor biodegradable in rat subcutaneous tissue. They were not osteoinductive in connective tissue either. However, in rat bone tissue β-W-doped α-TCP implants (TCP5W and TCP15W) were bioactive, biodegradable and osteoconductive. The rates of biodegradation and new bone formation observed for TCP5W and TCP15W implants in rat bone tissue were greater than for non-doped TCP.


2014 ◽  
Vol 73 (Suppl 2) ◽  
pp. 103.1-103
Author(s):  
S. Hong ◽  
E.-J. Lee ◽  
Y.J. Kim ◽  
B.S. Koo ◽  
E.-J. Chang ◽  
...  

2019 ◽  
Vol 14 (1) ◽  
pp. 147-159 ◽  
Author(s):  
Slobodan Vukicevic ◽  
Lovorka Grgurevic ◽  
Igor Erjavec ◽  
Marko Pecin ◽  
Tatjana Bordukalo‐Niksic ◽  
...  

2018 ◽  
Vol 24 (21-22) ◽  
pp. 1641-1651 ◽  
Author(s):  
Juliane D. Glaeser ◽  
Khosrowdad Salehi ◽  
Linda E.A. Kanim ◽  
Dmitriy Sheyn ◽  
Zachary NaPier ◽  
...  

2005 ◽  
Vol 288-289 ◽  
pp. 269-272
Author(s):  
Y. Yu ◽  
Jin Biao Chen ◽  
J.L. Yang ◽  
D.A.F. Morgan ◽  
W.R. Walsh

Deep-frozen morselized human bone grafts showed osteoconductivity and osteoinductivity when implanted into tibial window defects of nude rats. The osteoconductivity was assessed by measuring the total area of newly formed bone bridged by the implanted bone grafts in the entire defect area. The osteoinductivity was evidenced by the presence of active osteoblast-like cells and new bone formation around the implanted bone grafts, which were surrounded by soft tissues distant from the host cortex. Gamma irradiation at the doses of 15 or 25 kGray reduced the osteoconductivity (ANOVA and LSD tests, p<0.05) at 3 weeks post operation. The 25 kGray group had a significantly lower level of new bone formation compared with the 0 and 15 kGray groups. The evidences of osteoinductivity were only noted in the 0 and 15 kGray groups. Our data indicate that 25 kGray gamma irradiation reduces the osteoconductive and osteoinductive properties of the morselized human bone graft.


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