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The significance of DDR2 receptor in the skeleton growth of human being could not be ignored, which has revealed by analysis of rare genetic disease, chondrodysplasia termed as spondylometa-epiphyseal dysplasia (SMED-SL) with short limbs and abnormal calcifications. This Autosomal disease has been characterized by presence of short stature, short limbs, broad fingers, bone abnormalities and premature calcifications. These autosomal diseases caused by the occurrence of three missense mutations in DDR2 and one spliced site mutation were identified in eight patients from seven different consanguineous families [48]. The mutation caused in DDR2 receptor leading to SMED-SL was analyzed by carrying out experiment in the human cell line to realize the cellular and biochemical mechanism. The three-missense mutation in DDR2 resulting in trafficking defect making the DDR2 protein retained in endoplasmic reticulum whereas forth mutation resulted in DDR2, which is perfectly trafficked to the cell surface but failed to interact with collagen due to mutation in the key residue of collagen GW3965 [41]. Thus, the Autosomal disease SMED-SL is caused by at least two mutation leading to loss of function of DDR2 receptor that lack the ability to interact with collagen protein, resulting it in to severe skeleton abnormalities. This fact supports the essential contribution of DDR2 in human bone growth and developments. A current finding of DDR2 receptor contribution in the development of Murine Temporomandibular Joints (MTJ) has revealed by analyzing the primary culture of TMJ articular chondrocytes from wild type and DDR2slie/slie mice that showed abnormalities in chondrocytes maturity and mineralization in the absence of DDR2 [49]. This study also signifies the DDR2 is necessary for the normal development of TMJ condyle and maintain homeostasis of the extracellular matrix of joins. At the early stage of human developments, DDR2 receptor do contribute in bone growth and mineralization but mutation in this gene causes rare Autosomal diseases (SMED-SL) in a few cases where irregular mineralization is reported. It may be due to irregular/ lacks of regulatory mechanism involved in aberrant DDR2 expression and at late stage of life individual are prone to OA like condition. The mechanical stress, surgical damage etc. at joint tissue causes loss of extracellular matrix. The collagen that further binds DDR2 receptor in chondrocytes causes severe damage to cartilage by metalloproteinase’s but the intact pericellular matrix in turn protect DDR2 receptor being activated. Although DDR2 involve in bone development at early stage of life as per scientific report but due to changes in the pathophysiological condition of joints where DDR2 level gets incremented. Therefore, DDR2 seems to be dual mode of expression profile depending upon physiological condition and stages of life. It is also responsible for high expression at early stage of OA developments.