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Abhishek K.,Pandit Jawaharlal Nehru Memorial Medical College | Abhishek K.,Vinoba Bhave University | Kumar R.,Hamdard University | Arif E.,University of Pennsylvania | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2010

BMP-SMAD (bone morphogenetic protein) signaling pathways in association with APT play paramount roles in osteoblastic differentiation, bone formation and embryonic development of human and animals. However, the implications of potent components (BMP6, Smad1, Smad2 and APT) of this pathway in SCD (sickle cell disease) pathology with orthopedic complications (Ortho + SS) are poorly elucidated and substantially unknown. Here, we address the role of BMP6, Smad1, Smad2 and APT mRNA and protein expression in hMDDCs obtained from Ortho + SS patients, employing RT-PCR, qRT-PCR and immunoblotting. Interestingly, we observed that SCD pathology exhibited significantly up-regulated expression of those signaling components at the level of mRNA and protein. Furthermore, exogenous BMP6 induced apoptosis was observed to be significantly associated in Ortho + SS complication and markedly increased the percentage of cells undergoing apoptosis as compared to healthy group. Interestingly, the non-stimulated cells have shown higher apoptotic nuclei percentage than the stimulated cells in pathological condition. Thus, expression of BMP-SMAD signaling components augments apoptosis and up regulates the transcription of these genes and it suggests that induction is due to transcriptional regulation. Taken together, our findings provide evidence that BMP-SMAD signaling components along with APT were over expressed, mediates apoptosis and may play an important role in the SCD pathology with orthopedic complications. © 2010 Elsevier Inc. All rights reserved.


Abhishek K.,Pandit Jawaharlal Nehru Memorial Medical College | Sohail M.,Vinoba Bhave University | Zaidi A.,RMRIMS | Anwar S.,RMRIMS | And 4 more authors.
American Journal of Biochemistry and Biotechnology | Year: 2014

Background and objectives: Sickle cell disease has numerous consequences; one of the most characteristic is orthopedic complications. Bone Morphogenetic Proteins (BMPs) are involved in the various orthopedic complications and play important role in bone physiology influencing bone growth, turnover, bone formation and cartilage induction. We investigate a possible association of sickle cell disease with orthopedic disorders through BMP6 gene polymorphism. Methods: Among the population studied in Chhattisgarh and Jharkhand states (a total of 200 cases and 172 control groups), the association was examined between SNP 567C/G of BMP6 and orthopedic complications in sickling patients by employing PCR-RFLP and biochemical analysis. Results: 567C/G SNP has not been implicated in disease and doesn't increase the risk (OR = 1.27. OR = 0.85). We observed no significant association between the 567C/G polymorphism and case group in the studied population (P = 0.64, P = 0.91, respectively). However, significantly elevated Uric Acid (UA) level (P = 0.0001, P = 0.0001, P = 0.0001 and P = 0.0001, P = 0.0001, P = 0.0001 respectively) and Lactate Dehydrogenase (LDH) level (P = 0.0001, P = 0.0001, P = 0.0001 and P = 0.0001, P = 0.0001, P = 0.0001 respectively) in GG, CG and CC in case group as compared to control group among the studied population. Interpretation and Conclusions: 567C/G polymorphism in BMP6 gene is not associated with case group and in view of present observation, we suggest that evaluation of LDH and UA level and its association with polymorphisms in the BMP6 may be considered as a reliable molecular and biochemical markers possesses promising rational for diagnostic potential in clinical cases. © 2014 Science Publication.


Abhishek K.,Pandit Jawaharlal Nehru Memorial Medical College | Abhishek K.,Vinoba Bhave University | Sohail M.,National Institute of Malaria Research | Kumar R.,Hamdard University | And 2 more authors.
Clinica Chimica Acta | Year: 2010

Background: Bone morphogenetic protein (BMP) are involved in the various orthopedic complications such as avascular necrosis, osteonecrosis and bone turnover, therefore genes coding for proteins, like BMP4, can be potential candidate for studying orthopedic disorders. Methods: A case-control study was conducted to examine the association between SNP T538C of BMP4 and orthopedic complications in sickling patients by employing PCR-RFLP. Results: A total of 200 cases and 172 control groups were studied from Indian population. T538C SNP has not been implicated in disease and doesn't increase the risk (OR=0.89, OR=0.68). We observed no significant association between the T538C polymorphism and case group in the studied population. However, we observed significantly increased uric acid and LDH level in homowild (TT), heteromutant (TC) and homomutant (CC) in case group compared to control group ( all p=0.0001) and (p=0.0001, p=0.0001, p=0.015 and p=0.0001, p=0.0001, p=0.0001 respectively) in the studied population. Conclusions: The T/C polymorphism in BMP4 is not associated with case group and in view of present observation, we suggest that evaluation of LDH and uric acid level and its association with polymorphisms in the BMP4 may be considered to be reliable molecular and biochemical markers, and possess promising rational for diagnostic potential in clinical cases. © 2010 Elsevier B.V.


PubMed | Pandit Jawaharlal Nehru Memorial Medical College
Type: Journal Article | Journal: Clinica chimica acta; international journal of clinical chemistry | Year: 2010

Bone morphogenetic protein (BMP) are involved in the various orthopedic complications such as avascular necrosis, osteonecrosis and bone turnover, therefore genes coding for proteins, like BMP4, can be potential candidate for studying orthopedic disorders.A case-control study was conducted to examine the association between SNP T538C of BMP4 and orthopedic complications in sickling patients by employing PCR-RFLP.A total of 200 cases and 172 control groups were studied from Indian population. T538C SNP has not been implicated in disease and doesnt increase the risk (OR=0.89, OR=0.68). We observed no significant association between the T538C polymorphism and case group in the studied population. However, we observed significantly increased uric acid and LDH level in homowild (TT), heteromutant (TC) and homomutant (CC) in case group compared to control group ( all p=0.0001) and (p=0.0001, p=0.0001, p=0.015 and p=0.0001, p=0.0001, p=0.0001 respectively) in the studied population.The T/C polymorphism in BMP4 is not associated with case group and in view of present observation, we suggest that evaluation of LDH and uric acid level and its association with polymorphisms in the BMP4 may be considered to be reliable molecular and biochemical markers, and possess promising rational for diagnostic potential in clinical cases.

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