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- Publisher Website: 10.1016/j.matbio.2019.08.001
- Scopus: eid_2-s2.0-85070559795
- PMID: 31381970
- WOS: WOS:000501408200006
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Article: Disrupted type II collagenolysis impairs angiogenesis, delays endochondral ossification and initiates aberrant ossification in mouse limbs
Title | Disrupted type II collagenolysis impairs angiogenesis, delays endochondral ossification and initiates aberrant ossification in mouse limbs |
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Authors | |
Keywords | amino terminal sequence angiogenesis animal cell animal experiment animal model |
Issue Date | 2019 |
Publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/matbio |
Citation | Matrix Biology, 2019, v. 83, p. 77-96 How to Cite? |
Abstract | Cartilage remodelling and chondrocyte differentiation are tightly linked to angiogenesis during bone development and endochondral ossification. To investigate whether collagenase-mediated cleavage of the major cartilage collagen (collagen II) plays a role in this process, we generated a knockin mouse in which the mandatory collagenase cleavage site at PQG775↓776LAG, was mutated to PPG775↓776MPG (Col2a1Bailey). This approach blocked collagen II cleavage, and the production of putative collagen II matrikines derived from this site, without modifying matrix metalloproteinase expression or activity. We report here that this mouse (Bailey) is viable. It has a significantly expanded growth plate and exhibits delayed and abnormal angiogenic invasion into the growth plate. Deeper electron microscopy analyses revealed that, at around five weeks of age, a small number of blood vessel(s) penetrate into the growth plate, leading to its abrupt shrinking and the formation of a bony bridge. Our results from in vitro and ex vivo studies suggest that collagen II matrikines stimulate the normal branching of endothelial cells and promote blood vessel invasion at the chondro-osseous junction. The results further suggest that failed collagenolysis in Bailey leads to expansion of the hypertrophic zone and formation of a unique post-hypertrophic zone populated with chondrocytes that re-enter the cell cycle and proliferate. The biological rescue of this in vivo phenotype features the loss of a substantial portion of the growth plate through aberrant ossification, and narrowing of the remaining portion that leads to limb deformation. Together, these data suggest that collagen II matrikines stimulate angiogenesis in skeletal growth and development, revealing novel strategies for stimulating angiogenesis in other contexts such as fracture healing and surgical applications. |
Persistent Identifier | http://hdl.handle.net/10722/284298 |
ISSN | 2023 Impact Factor: 4.5 2023 SCImago Journal Rankings: 1.959 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Gauci, SJ | - |
dc.contributor.author | Golub, SB | - |
dc.contributor.author | Tatarczuch, L | - |
dc.contributor.author | Lee, E | - |
dc.contributor.author | Chan, D | - |
dc.contributor.author | Walsh, NC | - |
dc.contributor.author | Little, CB | - |
dc.contributor.author | Stanton, H | - |
dc.contributor.author | Lokmic, Z | - |
dc.contributor.author | Sims, NA | - |
dc.contributor.author | Mackie, EJ | - |
dc.contributor.author | Fosang, AJ | - |
dc.date.accessioned | 2020-07-20T05:57:36Z | - |
dc.date.available | 2020-07-20T05:57:36Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Matrix Biology, 2019, v. 83, p. 77-96 | - |
dc.identifier.issn | 0945-053X | - |
dc.identifier.uri | http://hdl.handle.net/10722/284298 | - |
dc.description.abstract | Cartilage remodelling and chondrocyte differentiation are tightly linked to angiogenesis during bone development and endochondral ossification. To investigate whether collagenase-mediated cleavage of the major cartilage collagen (collagen II) plays a role in this process, we generated a knockin mouse in which the mandatory collagenase cleavage site at PQG775↓776LAG, was mutated to PPG775↓776MPG (Col2a1Bailey). This approach blocked collagen II cleavage, and the production of putative collagen II matrikines derived from this site, without modifying matrix metalloproteinase expression or activity. We report here that this mouse (Bailey) is viable. It has a significantly expanded growth plate and exhibits delayed and abnormal angiogenic invasion into the growth plate. Deeper electron microscopy analyses revealed that, at around five weeks of age, a small number of blood vessel(s) penetrate into the growth plate, leading to its abrupt shrinking and the formation of a bony bridge. Our results from in vitro and ex vivo studies suggest that collagen II matrikines stimulate the normal branching of endothelial cells and promote blood vessel invasion at the chondro-osseous junction. The results further suggest that failed collagenolysis in Bailey leads to expansion of the hypertrophic zone and formation of a unique post-hypertrophic zone populated with chondrocytes that re-enter the cell cycle and proliferate. The biological rescue of this in vivo phenotype features the loss of a substantial portion of the growth plate through aberrant ossification, and narrowing of the remaining portion that leads to limb deformation. Together, these data suggest that collagen II matrikines stimulate angiogenesis in skeletal growth and development, revealing novel strategies for stimulating angiogenesis in other contexts such as fracture healing and surgical applications. | - |
dc.language | eng | - |
dc.publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/matbio | - |
dc.relation.ispartof | Matrix Biology | - |
dc.subject | amino terminal sequence | - |
dc.subject | angiogenesis | - |
dc.subject | animal cell | - |
dc.subject | animal experiment | - |
dc.subject | animal model | - |
dc.title | Disrupted type II collagenolysis impairs angiogenesis, delays endochondral ossification and initiates aberrant ossification in mouse limbs | - |
dc.type | Article | - |
dc.identifier.email | Chan, D: chand@hku.hk | - |
dc.identifier.authority | Chan, D=rp00540 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.matbio.2019.08.001 | - |
dc.identifier.pmid | 31381970 | - |
dc.identifier.scopus | eid_2-s2.0-85070559795 | - |
dc.identifier.hkuros | 311098 | - |
dc.identifier.volume | 83 | - |
dc.identifier.spage | 77 | - |
dc.identifier.epage | 96 | - |
dc.identifier.isi | WOS:000501408200006 | - |
dc.publisher.place | Netherlands | - |
dc.identifier.f1000 | 736348987 | - |
dc.identifier.issnl | 0945-053X | - |