Gene intervention in ligament and tendon: current status, challenges, future directions

Hildebrand, Kevin A.; Cb, Frank; Da, Hart

doi:10.1038/sj.gt.3302198

Cited by 79 publications

(51 citation statements)

References 59 publications

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“…The results obtained in group II were similar to the results reported by Hildebrand et al 7,9 At 0 weeks of remobilization (IIA), the average flexion contracture angle was 31.9 AE 10.28 on the operative side, as opposed Comparison between Groups I and II Angles measured on each operated knee were corrected for the normal baseline flexion contracture present on the nonoperative side (14.6 AE 6.08) in order to provide a more accurate comparison between the two groups (Fig. 4).…”

Section: Group IIsupporting

confidence: 82%

New rabbit knee model of posttraumatic joint contracture: Indirect capsular damage induces a severe contracture

Nesterenko

Morrey

Abdel

et al. 2009

Journal Orthopaedic Research

122

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Reported models of joint contracture fail to result in severe motion loss. Our purpose was to develop a rabbit model of knee contracture and compare it to another well-accepted model to determine if more severe stiffness can be achieved. Sixteen skeletally mature New Zealand White female rabbits had their right knee operated to create 3-mm defects on the noncartilaginous portions of the femoral condyles, hyperextend the joint to disrupt the posterior capsule, and immobilize the joint in maximum flexion with a Kirschner-wire for 8 weeks (group I). Sixteen additional rabbits were operated on using an identical protocol except for the absence of capsular injury (group II). In each group, mechanical testing was performed at the time of Kirschner-wire release in eight animals, and 16 weeks after remobilization in eight animals. At immobilization release, the average contracture was 76 AE 248 in group I versus 20 AE 108 in group II (p < 0.001). Sixteen weeks after remobilization, the mean contracture was 49 AE 158 group I versus 11 AE 108 in group II (p < 0.001). When associated with bone perforations and immobilization in forced flexion, injury to the posterior capsule results in a severe contracture in the rabbit knee. ß

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Section: Group IIsupporting

confidence: 82%

New rabbit knee model of posttraumatic joint contracture: Indirect capsular damage induces a severe contracture

Nesterenko

Morrey

Abdel

et al. 2009

Journal Orthopaedic Research

122

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“…However, normal ligaments and tendons are very similar in their compositions, with only certain minor variations. 72 Although these injuries have different pathologies, they do share a few extrinsic and intrinsic risk factors. It is therefore conceivable that they may also share, at least some, similar genetic risk factors.…”

Section: Tears Of the Rotator Cuff And Aclmentioning

confidence: 99%

Tendon and ligament injuries: the genetic component

September

Schwellnus²,

Collins³

2007

Br J Sports Med

133

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Tendons and ligaments within the upper and lower limbs are some of the more common sites of musculoskeletal injuries during physical activity. Several extrinsic and intrinsic factors have been shown to be associated with these injuries. More recently, studies have suggested that there is also, at least in part, a genetic component to the Achilles tendon, rotator cuff and anterior cruciate ligament injuries. However, specific genes have not been suggested to be associated with rotator cuff or anterior cruciate ligament injuries. Sequence variants of the tenascin C (TNC) gene, on the other hand, have been shown to be associated with Achilles tendinopathies and Achilles tendon ruptures, whereas a variant of the collagen V α 1 (COL5A1) gene has also been shown to be associated with Achilles tendinopathies. Both genes encode for important structural components of tendons and ligaments. TheCOL5A1gene encodes for a component of type V collagen, which has an important role in regulating collagen fibre assembly and fibre diameters. TheTNCgene, on the other hand, encodes for TNC, which regulates the tissue’s response to mechanical load. To date, only variants in two genes have been shown to be associated with Achilles tendon injuries. In addition, although specific genes have not been identified, investigators have suggested that there is also a genetic component to both rotator cuff and anterior cruciate ligament injuries. In future, specific genotypes associated with increased risk of injury to specific tendons and ligaments can prevent these injuries by identifying individuals at higher risk.

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“…Biochemical analyses were conducted of 1) hydroxyproline (Hyp), an imino acid marker used as an index of total collagen content measured by HPLC, 2) the mature collagen cross-link hydroxylysylpyridinoline (HP), which improves ECM strength and tissue quality in healing ligaments, also measured by HPLC, and 3) MCL cellularity by DNA measurement to assess the state of cell proliferation in the healing ligament. Real-time quantitative PCR gene markers were used to determine the upregulation or downregulation of specific genes that impact the ECM in healing MCLs as previously determined (15,18,19,32,34). To assess new collagen synthesis in remodeling ligament, the genes encoding collagen type I (Col1A2), collagen type III (Col3A1), and collagen type V (Col5a1) were assayed.…”

mentioning

confidence: 99%

Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading

Martinez¹,

Vailas²,

Vanderby³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Martinez DA, Vailas AC, Vanderby R Jr, Grindeland RE. Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading. Am J Physiol Regul Integr Comp Physiol 293: R1552-R1560, 2007. First published August 15, 2007 doi:10.1152/ajpregu.00423.2007.-Previous data from spaceflight studies indicate that injured muscle and bone heal slowly and abnormally compared with ground controls, strongly suggesting that ligaments or tendons may not repair optimally as well. Thus the objective of this study was to investigate the biochemical and molecular gene expression of the collagen extracellular matrix in response to medial collateral ligament (MCL) injury repair in hindlimb unloaded (HLU) rodents. Male rats were assigned to 3-and 7-wk treatment groups with three subgroups each: sham control, ambulatory healing (Amb-healing), and HLU-healing groups. Amb-and HLU-healing animals underwent bilateral surgical transection of their MCLs, whereas control animals were subjected to sham surgeries. All surgeries were performed under isoflurane anesthesia. After 3 wk or 7 wk of HLU, rats were euthanized and MCLs were surgically isolated and prepared for molecular or biochemical analyses. Hydroxyproline concentration and hydroxylysylpyridinoline collagen cross-link contents were measured by HPLC and showed a substantial decrement in surgical groups. MCL tissue cellularity, quantified by DNA content, remained significantly elevated in all HLU-healing groups vs. Amb-healing groups. MCL gene expression of collagen type I, collagen type III, collagen type V, fibronectin, decorin, biglycan, lysyl oxidase, matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-1, measured by real-time quantitative PCR, demonstrated differential expression in the HLU-healing groups compared with Ambhealing groups at both the 3-and 7-wk time points. Together, these data suggest that HLU affects dense fibrous connective tissue wound healing and confirms previous morphological and biomechanical data that HLU inhibits the ligament repair processes.

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Gene intervention in ligament and tendon: current status, challenges, future directions

Cited by 79 publications

References 59 publications

New rabbit knee model of posttraumatic joint contracture: Indirect capsular damage induces a severe contracture

New rabbit knee model of posttraumatic joint contracture: Indirect capsular damage induces a severe contracture

Tendon and ligament injuries: the genetic component

Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading

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